dbSNP rs1823475880: ADAM2:p.His681Tyr (chr8-39746605-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001464.5(ADAM2):c.2041C>T(p.His681Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000659 in 151,772 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H681D) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

ADAM2
NM_001464.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.177

Publications

0 publications found

Variant links:

Genes affected

ADAM2 (HGNC:198): (ADAM metallopeptidase domain 2) 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]

ADAM2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09986225).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAM2	NM_001464.5 link	c.2041C>T	p.His681Tyr	missense_variant	Exon 19 of 21	ENST00000265708.9	NP_001455.3	Q99965-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ADAM2	ENST00000265708.9 link	c.2041C>T	p.His681Tyr	missense_variant	Exon 19 of 21	1	NM_001464.5	ENSP00000265708.4	Q99965-1
ADAM2	ENST00000347580.8 link	c.1984C>T	p.His662Tyr	missense_variant	Exon 18 of 20	1		ENSP00000343854.4	Q99965-2
ADAM2	ENST00000379853.6 link	c.1573C>T	p.His525Tyr	missense_variant	Exon 15 of 17	1		ENSP00000369182.2	Q6P2G0
ADAM2	ENST00000521880.5 link	c.1852C>T	p.His618Tyr	missense_variant	Exon 18 of 20	2		ENSP00000429352.1	B4DWY7

Frequencies

GnomAD3 genomes

AF:

0.00000659

AC:

AN:

151772

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000659

AC:

AN:

151772

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74084

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41292

American (AMR)

AF:

0.00

AC:

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10514

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67938

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

0.051

(source)

DANN

Benign

0.42

DEOGEN2

Benign

0.086

.;.;T;T;T

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.0094

LIST_S2

Benign

0.59

T;T;T;T;.

M_CAP

Benign

0.018

MetaRNN

Benign

0.10

T;T;T;T;T

MetaSVM

Benign

-0.73

MutationAssessor

Benign

0.77

.;.;N;.;.

PhyloP100

-0.18

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.7

N;N;N;.;N

REVEL

Benign

0.17

Sift

Benign

0.45

T;T;T;.;T

Sift4G

Benign

0.28

T;T;T;T;T

Polyphen

0.0010

B;B;B;B;B

Vest4

0.27

MutPred

0.36

.;.;Loss of loop (P = 0.1242);.;.;

MVP

0.80

MPC

0.025

ClinPred

0.041

GERP RS

-4.7

Varity_R

0.027

gMVP

0.35

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over