Variant 12-108224777-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_014653.4(WSCD2):c.721G>A(p.Asp241Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000106 in 1,613,444 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000093 ( 2 hom. )

Consequence

WSCD2
NM_014653.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 2.07

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.02414596).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WSCD2	NM_014653.4 linkuse as main transcript	c.721G>A	p.Asp241Asn	missense_variant	5/9	ENST00000547525.6
LOC124903077	XR_007063583.1 linkuse as main transcript	n.182+9239C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WSCD2	ENST00000547525.6 linkuse as main transcript	c.721G>A	p.Asp241Asn	missense_variant	5/9	1	NM_014653.4	P1	Q2TBF2-1
WSCD2	ENST00000332082.8 linkuse as main transcript	c.721G>A	p.Asp241Asn	missense_variant	6/10	1		P1	Q2TBF2-1
WSCD2	ENST00000549903.1 linkuse as main transcript	c.721G>A	p.Asp241Asn	missense_variant	4/9	5			Q2TBF2-2
WSCD2	ENST00000551638.5 linkuse as main transcript	c.262G>A	p.Asp88Asn	missense_variant	4/5	4

Frequencies

GnomAD3 genomes

AF:

0.000223

AC:

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000964

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000981

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00173

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.000125

AC:

AN:

248622

Hom.:

AF XY:

0.000141

AC XY:

AN XY:

134962

show subpopulations

Gnomad AFR exome

AF:

0.000129

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00117

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000265

Gnomad OTH exome

AF:

0.000661

GnomAD4 exome

AF:

0.0000931

AC:

136

AN:

1461092

Hom.:

Cov.:

AF XY:

0.0000867

AC XY:

AN XY:

726878

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000756

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.0000380

Gnomad4 NFE exome

AF:

0.0000486

Gnomad4 OTH exome

AF:

0.000712

GnomAD4 genome

AF:

0.000230

AC:

AN:

152352

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.000980

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00174

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.0000995

Hom.:

Bravo

AF:

0.000212

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000132

AC:

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 15, 2022

The c.721G>A (p.D241N) alteration is located in exon 5 (coding exon 4) of the WSCD2 gene. This alteration results from a G to A substitution at nucleotide position 721, causing the aspartic acid (D) at amino acid position 241 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Nov 03, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.61

Cadd

Benign

9.8

Dann

Uncertain

0.98

DEOGEN2

Benign

0.017

T;.;T;.

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.55

FATHMM_MKL

Uncertain

0.87

M_CAP

Benign

0.0070

MetaRNN

Benign

0.024

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

M;.;M;M

MutationTaster

Benign

0.57

D;D;D;D

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.7

N;N;N;N

REVEL

Benign

0.094

Sift

Benign

0.19

T;T;T;T

Sift4G

Benign

0.10

T;T;T;T

Polyphen

0.0

B;.;B;.

Vest4

0.068

MVP

0.10

MPC

0.37

ClinPred

0.067

GERP RS

-0.71

Varity_R

0.043

gMVP

0.63

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