Variant 12-108195870-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014653.4(WSCD2):c.38G>A(p.Arg13His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000297 in 1,613,704 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000029 ( 0 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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WSCD2	NM_014653.4 linkuse as main transcript	c.38G>A	p.Arg13His	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.38G>A	p.Arg13His	missense_variant	2/9	1	NM_014653.4	ENSP00000448047.1	Q2TBF2-1
WSCD2	ENST00000332082.8 linkuse as main transcript	c.38G>A	p.Arg13His	missense_variant	3/10	1		ENSP00000331933.4	Q2TBF2-1
WSCD2	ENST00000549903.1 linkuse as main transcript	c.38G>A	p.Arg13His	missense_variant	1/9	5		ENSP00000447272.1	Q2TBF2-2
WSCD2	ENST00000551638.5 linkuse as main transcript	c.-77-10419G>A		intron_variant		4		ENSP00000446744.1	F8W030

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000161

AC:

AN:

247854

Hom.:

AF XY:

0.0000223

AC XY:

AN XY:

134680

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000111

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000178

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000294

AC:

AN:

1461544

Hom.:

Cov.:

AF XY:

0.0000316

AC XY:

AN XY:

727048

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000333

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152160

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000340

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

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

Mar 15, 2024

The c.38G>A (p.R13H) 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 38, causing the arginine (R) at amino acid position 13 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

0.21

BayesDel_addAF

Uncertain

0.021

BayesDel_noAF

Uncertain

0.020

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.29

T;T;.

Eigen

Pathogenic

0.92

Eigen_PC

Pathogenic

0.91

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.96

.;D;D

M_CAP

Benign

0.031

MetaRNN

Uncertain

0.61

D;D;D

MetaSVM

Benign

-0.56

MutationAssessor

Uncertain

2.1

M;M;M

PrimateAI

Uncertain

0.58

PROVEAN

Uncertain

-3.0

D;D;D

REVEL

Uncertain

0.45

Sift

Uncertain

0.0030

D;D;D

Sift4G

Uncertain

0.0070

D;D;D

Polyphen

1.0

D;D;.

Vest4

0.61

MutPred

0.57

Gain of catalytic residue at K15 (P = 0);Gain of catalytic residue at K15 (P = 0);Gain of catalytic residue at K15 (P = 0);

MVP

0.39

MPC

1.3

ClinPred

0.92

GERP RS

5.7

Varity_R

0.48

gMVP

0.58

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