Variant 12-108224790-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014653.4(WSCD2):c.734T>A(p.Leu245Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000013 in 1,613,734 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

WSCD2
NM_014653.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.06

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14889354).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WSCD2	NM_014653.4 linkuse as main transcript	c.734T>A	p.Leu245Gln	missense_variant	5/9	ENST00000547525.6
LOC124903077	XR_007063583.1 linkuse as main transcript	n.182+9226A>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.734T>A	p.Leu245Gln	missense_variant	5/9	1	NM_014653.4	P1	Q2TBF2-1
WSCD2	ENST00000332082.8 linkuse as main transcript	c.734T>A	p.Leu245Gln	missense_variant	6/10	1		P1	Q2TBF2-1
WSCD2	ENST00000549903.1 linkuse as main transcript	c.734T>A	p.Leu245Gln	missense_variant	4/9	5			Q2TBF2-2
WSCD2	ENST00000551638.5 linkuse as main transcript	c.275T>A	p.Leu92Gln	missense_variant	4/5	4

Frequencies

GnomAD3 genomes

AF:

0.0000722

AC:

AN:

152252

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000281

AC:

AN:

248912

Hom.:

AF XY:

0.00000740

AC XY:

AN XY:

135092

show subpopulations

Gnomad AFR exome

AF:

0.000323

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1461364

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727008

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000853

AC:

AN:

152370

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74514

show subpopulations

Gnomad4 AFR

AF:

0.000289

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:

0.00

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.0000252

Hom.:

Bravo

AF:

0.0000453

ESP6500AA

AF:

0.000519

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000248

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Oct 03, 2022

The c.734T>A (p.L245Q) alteration is located in exon 5 (coding exon 4) of the WSCD2 gene. This alteration results from a T to A substitution at nucleotide position 734, causing the leucine (L) at amino acid position 245 to be replaced by a glutamine (Q). 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

0.078

BayesDel_addAF

Benign

-0.013

BayesDel_noAF

Uncertain

0.050

Cadd

Benign

Dann

Benign

0.75

DEOGEN2

Benign

0.0092

T;.;T;.

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Pathogenic

0.97

M_CAP

Benign

0.036

MetaRNN

Benign

0.15

T;T;T;T

MetaSVM

Benign

-0.81

MutationAssessor

Benign

1.7

L;.;L;L

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.56

PROVEAN

Benign

0.19

N;N;N;N

REVEL

Benign

0.25

Sift

Benign

0.64

T;T;T;T

Sift4G

Benign

0.41

T;T;T;T

Polyphen

0.96

D;.;D;.

Vest4

0.62

MVP

0.45

MPC

1.1

ClinPred

0.14

GERP RS

5.4

Varity_R

0.19

gMVP

0.81

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