Variant 12-108224853-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_014653.4(WSCD2):c.797C>T(p.Thr266Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.262 in 1,612,852 control chromosomes in the GnomAD database, including 60,509 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.21 ( 4616 hom., cov: 34)

Exomes 𝑓: 0.27 ( 55893 hom. )

Consequence

WSCD2
NM_014653.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.70

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 Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.136928E-4).

BP6

Variant 12-108224853-C-T is Benign according to our data. Variant chr12-108224853-C-T is described in ClinVar as [Benign]. Clinvar id is 1233855.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.525 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WSCD2	NM_014653.4 linkuse as main transcript	c.797C>T	p.Thr266Ile	missense_variant	5/9	ENST00000547525.6
LOC124903077	XR_007063583.1 linkuse as main transcript	n.182+9163G>A		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.797C>T	p.Thr266Ile	missense_variant	5/9	1	NM_014653.4	P1	Q2TBF2-1
WSCD2	ENST00000332082.8 linkuse as main transcript	c.797C>T	p.Thr266Ile	missense_variant	6/10	1		P1	Q2TBF2-1
WSCD2	ENST00000549903.1 linkuse as main transcript	c.797C>T	p.Thr266Ile	missense_variant	4/9	5			Q2TBF2-2
WSCD2	ENST00000551638.5 linkuse as main transcript	c.338C>T	p.Thr113Ile	missense_variant	4/5	4

Frequencies

GnomAD3 genomes

AF:

0.212

AC:

32228

AN:

152120

Hom.:

4612

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0459

Gnomad AMI

AF:

0.228

Gnomad AMR

AF:

0.165

Gnomad ASJ

AF:

0.249

Gnomad EAS

AF:

0.541

Gnomad SAS

AF:

0.355

Gnomad FIN

AF:

0.338

Gnomad MID

AF:

0.152

Gnomad NFE

AF:

0.267

Gnomad OTH

AF:

0.204

GnomAD3 exomes

AF:

0.268

AC:

66361

AN:

247790

Hom.:

10525

AF XY:

0.273

AC XY:

36718

AN XY:

134440

show subpopulations

Gnomad AFR exome

AF:

0.0403

Gnomad AMR exome

AF:

0.158

Gnomad ASJ exome

AF:

0.241

Gnomad EAS exome

AF:

0.546

Gnomad SAS exome

AF:

0.321

Gnomad FIN exome

AF:

0.341

Gnomad NFE exome

AF:

0.263

Gnomad OTH exome

AF:

0.264

GnomAD4 exome

AF:

0.268

AC:

390745

AN:

1460614

Hom.:

55893

Cov.:

AF XY:

0.271

AC XY:

196623

AN XY:

726590

show subpopulations

Gnomad4 AFR exome

AF:

0.0369

Gnomad4 AMR exome

AF:

0.157

Gnomad4 ASJ exome

AF:

0.244

Gnomad4 EAS exome

AF:

0.520

Gnomad4 SAS exome

AF:

0.322

Gnomad4 FIN exome

AF:

0.345

Gnomad4 NFE exome

AF:

0.263

Gnomad4 OTH exome

AF:

0.270

GnomAD4 genome

AF:

0.212

AC:

32242

AN:

152238

Hom.:

4616

Cov.:

AF XY:

0.220

AC XY:

16350

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.0457

Gnomad4 AMR

AF:

0.166

Gnomad4 ASJ

AF:

0.249

Gnomad4 EAS

AF:

0.542

Gnomad4 SAS

AF:

0.354

Gnomad4 FIN

AF:

0.338

Gnomad4 NFE

AF:

0.267

Gnomad4 OTH

AF:

0.211

Alfa

AF:

0.256

Hom.:

11289

Bravo

AF:

0.190

TwinsUK

AF:

0.254

AC:

941

ALSPAC

AF:

0.254

AC:

980

ESP6500AA

AF:

0.0483

AC:

193

ESP6500EA

AF:

0.257

AC:

2151

ExAC

AF:

0.269

AC:

32480

Asia WGS

AF:

0.442

AC:

1537

AN:

3478

EpiCase

AF:

0.255

EpiControl

AF:

0.261

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 13, 2018

This variant is associated with the following publications: (PMID: 30389748, 29632382) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.78

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Uncertain

-0.040

Cadd

Pathogenic

Dann

Uncertain

1.0

DEOGEN2

Benign

0.025

T;.;T;.

Eigen

Pathogenic

0.76

Eigen_PC

Pathogenic

0.76

FATHMM_MKL

Pathogenic

0.98

MetaRNN

Benign

0.00081

T;T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Uncertain

2.2

M;.;M;M

MutationTaster

Benign

6.3e-9

P;P;P;P

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-2.3

N;D;N;N

REVEL

Benign

0.19

Sift

Benign

0.054

T;D;T;T

Sift4G

Uncertain

0.0080

D;D;D;D

Polyphen

1.0

D;.;D;D

Vest4

0.42

MPC

1.2

ClinPred

0.017

GERP RS

5.4

Varity_R

0.30

gMVP

0.68

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