10-50093306-G-T

Variant names:

• chr10-50093306-G-T
• rs1554883535
• NM_001005751.3:c.1042G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001005751.3(WASHC2A):​c.1042G>T​(p.Asp348Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000279 in 1,433,938 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D348N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000081 (0 hom., cov: 16)
  • Exomes 𝑓: 0.0000023 (0 hom.)
• Consequence: WASHC2A NM_001005751.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.86

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]

ACMG classification

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=0.2624301).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WASHC2A	NM_001005751.3	c.1042G>T	p.Asp348Tyr	missense_variant	Exon 12 of 31	ENST00000282633.10	NP_001005751.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WASHC2A	ENST00000282633.10	c.1042G>T	p.Asp348Tyr	missense_variant	Exon 12 of 31	1	NM_001005751.3	ENSP00000282633.5

Frequencies

GnomAD3 genomes AF: 0.00000805 AC: 1 AN: 124192 Hom.: 0 Cov.: 16

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000271

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000229 AC: 3 AN: 1309746 Hom.: 0 Cov.: 27 AF XY: 0.00000305 AC XY: 2 AN XY: 655462

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000363

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000805 AC: 1 AN: 124192 Hom.: 0 Cov.: 16 AF XY: 0.0000168 AC XY: 1 AN XY: 59648

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000271

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.23	.;.;T;T;.
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Pathogenic	0.97	D;D;D;D;D
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.26	T;T;T;T;T
MetaSVM	Uncertain	-0.012	T
PrimateAI	Uncertain	0.77	T
PROVEAN	Pathogenic	-7.6	.;D;D;D;D
REVEL	Uncertain	0.35
Sift	Uncertain	0.0010	.;D;D;D;D
Sift4G	Uncertain	0.0020	D;D;D;D;D
Polyphen		1.0	.;D;D;D;D
Vest4		0.42
MutPred		0.26		.;Loss of loop (P = 0.0374);Loss of loop (P = 0.0374);Loss of loop (P = 0.0374);.;
MVP		0.068
ClinPred		1.0	D
GERP RS		4.5
Varity_R		0.86
gMVP		0.44

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

Other links and lift over

dbSNP: rs1554883535; hg19: chr10-51853066;