Variant 10-50095689-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001005751.3(WASHC2A):c.1331G>A(p.Gly444Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 1,602,712 control chromosomes in the GnomAD database, including 46,993 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.26 ( 5166 hom., cov: 27)

Exomes 𝑓: 0.23 ( 41827 hom. )

Consequence

WASHC2A
NM_001005751.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.647

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016828179).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.607 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.1331G>A	p.Gly444Asp	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.1331G>A	p.Gly444Asp	missense_variant	15/31	1	NM_001005751.3	ENSP00000282633.5		Q641Q2-1

Frequencies

GnomAD3 genomes

AF:

0.255

AC:

38292

AN:

150106

Hom.:

5160

Cov.:

show subpopulations

Gnomad AFR

AF:

0.304

Gnomad AMI

AF:

0.164

Gnomad AMR

AF:

0.237

Gnomad ASJ

AF:

0.205

Gnomad EAS

AF:

0.626

Gnomad SAS

AF:

0.342

Gnomad FIN

AF:

0.247

Gnomad MID

AF:

0.212

Gnomad NFE

AF:

0.201

Gnomad OTH

AF:

0.269

GnomAD3 exomes

AF:

0.413

AC:

39142

AN:

94886

Hom.:

13494

AF XY:

0.410

AC XY:

20808

AN XY:

50710

show subpopulations

Gnomad AFR exome

AF:

0.452

Gnomad AMR exome

AF:

0.321

Gnomad ASJ exome

AF:

0.283

Gnomad EAS exome

AF:

0.928

Gnomad SAS exome

AF:

0.500

Gnomad FIN exome

AF:

0.405

Gnomad NFE exome

AF:

0.311

Gnomad OTH exome

AF:

0.387

GnomAD4 exome

AF:

0.231

AC:

335839

AN:

1452486

Hom.:

41827

Cov.:

AF XY:

0.233

AC XY:

168354

AN XY:

722328

show subpopulations

Gnomad4 AFR exome

AF:

0.302

Gnomad4 AMR exome

AF:

0.221

Gnomad4 ASJ exome

AF:

0.215

Gnomad4 EAS exome

AF:

0.646

Gnomad4 SAS exome

AF:

0.333

Gnomad4 FIN exome

AF:

0.243

Gnomad4 NFE exome

AF:

0.205

Gnomad4 OTH exome

AF:

0.254

GnomAD4 genome

AF:

0.255

AC:

38335

AN:

150226

Hom.:

5166

Cov.:

AF XY:

0.260

AC XY:

19076

AN XY:

73300

show subpopulations

Gnomad4 AFR

AF:

0.304

Gnomad4 AMR

AF:

0.238

Gnomad4 ASJ

AF:

0.205

Gnomad4 EAS

AF:

0.626

Gnomad4 SAS

AF:

0.343

Gnomad4 FIN

AF:

0.247

Gnomad4 NFE

AF:

0.201

Gnomad4 OTH

AF:

0.272

Alfa

AF:

0.0510

Hom.:

Bravo

AF:

0.259

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

Apr 01, 2022

The c.1331G>A (p.G444D) alteration is located in exon 15 (coding exon 15) of the FAM21A gene. This alteration results from a G to A substitution at nucleotide position 1331, causing the glycine (G) at amino acid position 444 to be replaced by an aspartic acid (D). 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

0.098

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

0.31

DANN

Benign

0.34

DEOGEN2

Benign

0.019

.;.;T;T;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0073

LIST_S2

Benign

0.27

T;T;T;T;T

M_CAP

Benign

0.0029

MetaRNN

Benign

0.0017

T;T;T;T;T

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.3

.;N;N;N;N

REVEL

Benign

0.058

Sift

Benign

0.19

.;T;T;T;T

Sift4G

Benign

0.64

T;T;T;T;T

Polyphen

0.10, 0.23, 0.0010

.;B;B;B;B

Vest4

0.070

MutPred

0.096

.;Loss of glycosylation at P446 (P = 0.0789);Loss of glycosylation at P446 (P = 0.0789);Loss of glycosylation at P446 (P = 0.0789);.;

MVP

0.043

ClinPred

0.018

GERP RS

-4.5

Varity_R

0.080

gMVP

0.081

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