Variant 10-50095760-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_001005751.3(WASHC2A):c.1402A>T(p.Ser468Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0311 in 146,570 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.031 ( 0 hom., cov: 26)

Exomes 𝑓: 0.023 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

WASHC2A
NM_001005751.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.00

Variant links:

Genes affected

WASHC2A (HGNC:23416): (WASH complex subunit 2A) Predicted to enable phosphatidylinositol phosphate binding activity and retromer complex binding activity. Involved in protein localization to endosome. Located in cytosol and nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

WASHC2A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.24855056).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0559 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WASHC2A	NM_001005751.3 linkuse as main transcript	c.1402A>T	p.Ser468Cys	missense_variant	15/31	ENST00000282633.10	NP_001005751.1	Q641Q2-1Q6P0Q7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WASHC2A	ENST00000282633.10 linkuse as main transcript	c.1402A>T	p.Ser468Cys	missense_variant	15/31	1	NM_001005751.3	ENSP00000282633.5		Q641Q2-1

Frequencies

GnomAD3 genomes

AF:

0.0311

AC:

4548

AN:

146458

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0576

Gnomad AMI

AF:

0.0167

Gnomad AMR

AF:

0.0221

Gnomad ASJ

AF:

0.0120

Gnomad EAS

AF:

0.0325

Gnomad SAS

AF:

0.0135

Gnomad FIN

AF:

0.0204

Gnomad MID

AF:

0.0161

Gnomad NFE

AF:

0.0218

Gnomad OTH

AF:

0.0276

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0233

AC:

33121

AN:

1421288

Hom.:

Cov.:

AF XY:

0.0225

AC XY:

15912

AN XY:

706856

show subpopulations

Gnomad4 AFR exome

AF:

0.0628

Gnomad4 AMR exome

AF:

0.00819

Gnomad4 ASJ exome

AF:

0.0110

Gnomad4 EAS exome

AF:

0.0289

Gnomad4 SAS exome

AF:

0.0103

Gnomad4 FIN exome

AF:

0.0194

Gnomad4 NFE exome

AF:

0.0241

Gnomad4 OTH exome

AF:

0.0229

GnomAD4 genome

AF:

0.0311

AC:

4562

AN:

146570

Hom.:

Cov.:

AF XY:

0.0305

AC XY:

2189

AN XY:

71704

show subpopulations

Gnomad4 AFR

AF:

0.0579

Gnomad4 AMR

AF:

0.0220

Gnomad4 ASJ

AF:

0.0120

Gnomad4 EAS

AF:

0.0323

Gnomad4 SAS

AF:

0.0133

Gnomad4 FIN

AF:

0.0204

Gnomad4 NFE

AF:

0.0218

Gnomad4 OTH

AF:

0.0273

Alfa

AF:

0.0387

Hom.:

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

Jun 13, 2022

The c.1402A>T (p.S468C) alteration is located in exon 15 (coding exon 15) of the FAM21A gene. This alteration results from a A to T substitution at nucleotide position 1402, causing the serine (S) at amino acid position 468 to be replaced by a cysteine (C). 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

0.076

BayesDel_addAF

Benign

-0.027

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.15

.;.;T;T;.

Eigen

Uncertain

0.33

Eigen_PC

Benign

0.22

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.84

T;D;D;D;D

M_CAP

Benign

0.0087

MetaRNN

Benign

0.25

T;T;T;T;T

MetaSVM

Benign

-0.63

PrimateAI

Uncertain

0.51

PROVEAN

Uncertain

-3.5

.;D;D;D;D

REVEL

Benign

0.16

Sift

Uncertain

0.0010

.;D;D;D;D

Sift4G

Uncertain

0.0060

D;D;D;D;D

Polyphen

1.0, 1.0, 1.0

.;D;D;D;D

Vest4

0.19

MutPred

0.12

.;Loss of glycosylation at S468 (P = 0.016);Loss of glycosylation at S468 (P = 0.016);Loss of glycosylation at S468 (P = 0.016);.;

MVP

0.15

ClinPred

0.96

GERP RS

4.7

Varity_R

0.33

gMVP

0.097

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