Variant chr2-206445411-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_003812.4(ADAM23):c.319A>G(p.Met107Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00142 in 1,614,160 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00083 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 8 hom. )

Consequence

ADAM23
NM_003812.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.761

Variant links:

Genes affected

ADAM23 (HGNC:202): (ADAM metallopeptidase domain 23) 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. It is reported that inactivation of this gene is associated with tumorigenesis in human cancers. [provided by RefSeq, May 2013]

ADAM23 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0060574114).

BP6

Variant 2-206445411-A-G is Benign according to our data. Variant chr2-206445411-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 790343.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 127 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAM23	NM_003812.4 linkuse as main transcript	c.319A>G	p.Met107Val	missense_variant	2/26	ENST00000264377.8	NP_003803.1	O75077-1A0A024R3W8
ADAM23	NM_001410985.1 linkuse as main transcript	c.319A>G	p.Met107Val	missense_variant	2/26		NP_001397914.1
ADAM23	XM_005246932.4 linkuse as main transcript	c.319A>G	p.Met107Val	missense_variant	2/25		XP_005246989.1	O75077-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAM23	ENST00000264377.8 linkuse as main transcript	c.319A>G	p.Met107Val	missense_variant	2/26	1	NM_003812.4	ENSP00000264377.3		O75077-1
ADAM23	ENST00000374415.7 linkuse as main transcript	c.319A>G	p.Met107Val	missense_variant	2/26	5		ENSP00000363536.3		E7EWD3

Frequencies

GnomAD3 genomes

AF:

0.000828

AC:

126

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00122

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.00130

AC:

328

AN:

251450

Hom.:

AF XY:

0.00149

AC XY:

203

AN XY:

135898

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.000954

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00252

Gnomad FIN exome

AF:

0.000416

Gnomad NFE exome

AF:

0.00169

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.00148

AC:

2169

AN:

1461816

Hom.:

Cov.:

AF XY:

0.00152

AC XY:

1106

AN XY:

727202

show subpopulations

Gnomad4 AFR exome

AF:

0.000358

Gnomad4 AMR exome

AF:

0.00105

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00236

Gnomad4 FIN exome

AF:

0.000524

Gnomad4 NFE exome

AF:

0.00161

Gnomad4 OTH exome

AF:

0.00111

GnomAD4 genome

AF:

0.000834

AC:

127

AN:

152344

Hom.:

Cov.:

AF XY:

0.000819

AC XY:

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.000313

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.00123

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.00139

Hom.:

Bravo

AF:

0.000903

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00151

AC:

ExAC

AF:

0.00138

AC:

168

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00158

EpiControl

AF:

0.00249

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.70

CADD

Benign

5.1

DANN

Benign

0.39

DEOGEN2

Benign

0.061

T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.45

LIST_S2

Benign

0.47

T;T

M_CAP

Benign

0.0087

MetaRNN

Benign

0.0061

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-1.1

N;.

PrimateAI

Benign

0.26

PROVEAN

Benign

0.12

N;N

REVEL

Benign

0.050

Sift

Benign

0.78

T;T

Sift4G

Benign

0.68

T;T

Polyphen

0.0

B;.

Vest4

0.13

MVP

0.11

MPC

0.053

ClinPred

0.0040

GERP RS

-2.8

Varity_R

0.051

gMVP

0.29

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over