ADAM2

Chr 8

ADAM metallopeptidase domain 2

Also known as: CRYN1, CRYN2, CT15, FTNB, PH-30b, PH30, PH30-beta

NCBI Gene: 2515 ENSG00000104755 UniProt: Q99965 OMIM: 601533

This gene encodes a member of the ADAM (a disintegrin and metalloprotease domain) family. Members of this family are membrane-anchored proteins structurally related to snake venom disintegrins, and have been implicated in a variety of biological processes involving cell-cell and cell-matrix interactions, including fertilization, muscle development, and neurogenesis. The encoded protein is a subunit of an integral sperm membrane glycoprotein called fertilin, which plays an important role in sperm-egg interactions. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, May 2013]

OMIM Research

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.18

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.18LOEUF

pLI 0.000

Z-score 0.65

OE 0.89 (0.68–1.18)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.65Z-score

OE missense 1.09 (1.01–1.19)

413 obs / 377.4 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.89 (0.68–1.18)

0≤0.351.4

Missense OE?1.09 (1.01–1.19)

0≤0.61.4

Synonymous OE?1.12

0≤1.21.6

LoF obs/exp: 36 / 40.4Missense obs/exp: 413 / 377.4Syn Z: -1.08

Background carrier burden — how many people carry a rare variant somewhere in ADAM2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 50

1,024 rare PASS variants

Rare truncating (LoF)

1 in 240

203 rare PASS variants

Rare synonymous (reference)

1 in 160

336 rare PASS variants

Rare missense and truncating variants are carried at similar rates in ADAM2; this gene does not show strong loss-of-function constraint by this measure. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 88	1 in 500
South Asian	~43k	1 in 43	1 in 230
Remaining (unassigned)	~30k	1 in 37	1 in 220
European (Finnish)	~27k	1 in 200	1 in 510
Admixed American	~22k	1 in 47	1 in 320
African / African American	~21k	1 in 50	1 in 330
East Asian	~20k	1 in 53	1 in 320
Ashkenazi Jewish	~13k	1 in 210	1 in 1,200
Middle Eastern	~2,884	1 in 48	1 in 410

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.