Variant chr2-206542092-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_003812.4(ADAM23):c.614T>C(p.Val205Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000533 in 1,614,036 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000055 ( 2 hom. )

Consequence

ADAM23
NM_003812.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.63

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.14694801).

BS2

High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAM23	NM_003812.4 linkuse as main transcript	c.614T>C	p.Val205Ala	missense_variant	5/26	ENST00000264377.8	NP_003803.1	O75077-1A0A024R3W8
ADAM23	NM_001410985.1 linkuse as main transcript	c.614T>C	p.Val205Ala	missense_variant	5/26		NP_001397914.1
ADAM23	XM_005246932.4 linkuse as main transcript	c.614T>C	p.Val205Ala	missense_variant	5/25		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.614T>C	p.Val205Ala	missense_variant	5/26	1	NM_003812.4	ENSP00000264377.3		O75077-1
ADAM23	ENST00000374415.7 linkuse as main transcript	c.614T>C	p.Val205Ala	missense_variant	5/26	5		ENSP00000363536.3		E7EWD3

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000875

AC:

AN:

251450

Hom.:

AF XY:

0.0000957

AC XY:

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000555

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000547

AC:

AN:

1461866

Hom.:

Cov.:

AF XY:

0.0000715

AC XY:

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000603

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000126

Gnomad4 OTH exome

AF:

0.000132

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152170

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000675

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000741

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 07, 2024

The c.614T>C (p.V205A) alteration is located in exon 5 (coding exon 5) of the ADAM23 gene. This alteration results from a T to C substitution at nucleotide position 614, causing the valine (V) at amino acid position 205 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.59

DEOGEN2

Benign

0.095

T;T

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.28

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.44

T;T

M_CAP

Benign

0.0056

MetaRNN

Benign

0.15

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

L;.

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.90

N;N

REVEL

Benign

0.088

Sift

Benign

0.51

T;T

Sift4G

Benign

0.53

T;T

Polyphen

0.051

B;.

Vest4

0.41

MutPred

0.60

Loss of stability (P = 0.0101);Loss of stability (P = 0.0101);

MVP

0.21

MPC

0.095

ClinPred

0.053

GERP RS

5.1

Varity_R

0.077

gMVP

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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