Variant 12-108195885-G-A 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_014653.4(WSCD2):c.53G>A(p.Arg18His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00093 in 1,614,082 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00061 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00096 ( 2 hom. )

Consequence

WSCD2
NM_014653.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.54

Variant links:

Genes affected

WSCD2 (HGNC:29117): (WSC domain containing 2) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

WSCD2 links:

LOC124903077 (HGNC:):

LOC124903077 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1852529).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WSCD2	NM_014653.4 linkuse as main transcript	c.53G>A	p.Arg18His	missense_variant	2/9	ENST00000547525.6	NP_055468.2	Q2TBF2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
WSCD2	ENST00000547525.6 linkuse as main transcript	c.53G>A	p.Arg18His	missense_variant	2/9	1	NM_014653.4	ENSP00000448047.1	Q2TBF2-1
WSCD2	ENST00000332082.8 linkuse as main transcript	c.53G>A	p.Arg18His	missense_variant	3/10	1		ENSP00000331933.4	Q2TBF2-1
WSCD2	ENST00000549903.1 linkuse as main transcript	c.53G>A	p.Arg18His	missense_variant	1/9	5		ENSP00000447272.1	Q2TBF2-2
WSCD2	ENST00000551638.5 linkuse as main transcript	c.-77-10404G>A		intron_variant		4		ENSP00000446744.1	F8W030

Frequencies

GnomAD3 genomes

AF:

0.000611

AC:

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00106

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000643

AC:

160

AN:

248774

Hom.:

AF XY:

0.000637

AC XY:

AN XY:

135060

show subpopulations

Gnomad AFR exome

AF:

0.000261

Gnomad AMR exome

AF:

0.000203

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.0000931

Gnomad NFE exome

AF:

0.00123

Gnomad OTH exome

AF:

0.000662

GnomAD4 exome

AF:

0.000963

AC:

1408

AN:

1461788

Hom.:

Cov.:

AF XY:

0.000967

AC XY:

703

AN XY:

727196

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.000246

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000139

Gnomad4 FIN exome

AF:

0.0000937

Gnomad4 NFE exome

AF:

0.00120

Gnomad4 OTH exome

AF:

0.000580

GnomAD4 genome

AF:

0.000611

AC:

AN:

152294

Hom.:

Cov.:

AF XY:

0.000591

AC XY:

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00106

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000922

Hom.:

Bravo

AF:

0.000589

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000503

AC:

ESP6500EA

AF:

0.000600

AC:

ExAC

AF:

0.000719

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00109

EpiControl

AF:

0.00113

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

Aug 13, 2021

The c.53G>A (p.R18H) alteration is located in exon 2 (coding exon 1) of the WSCD2 gene. This alteration results from a G to A substitution at nucleotide position 53, causing the arginine (R) at amino acid position 18 to be replaced by a histidine (H). 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

0.28

BayesDel_addAF

Benign

-0.081

BayesDel_noAF

Uncertain

0.070

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.061

T;T;.

Eigen

Pathogenic

0.90

Eigen_PC

Pathogenic

0.90

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.96

.;D;D

M_CAP

Benign

0.016

MetaRNN

Benign

0.19

T;T;T

MetaSVM

Benign

-0.80

MutationAssessor

Uncertain

2.1

M;M;M

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-1.8

N;N;N

REVEL

Uncertain

0.35

Sift

Uncertain

0.015

D;D;D

Sift4G

Uncertain

0.020

D;D;D

Polyphen

1.0

D;D;.

Vest4

0.72

MVP

0.33

MPC

1.3

ClinPred

0.070

GERP RS

5.7

Varity_R

0.27

gMVP

0.61

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