10-50093890-C-T

Variant names:

• chr10-50093890-C-T
• rs1422696859
• NM_001005751.3:c.1153C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001005751.3(WASHC2A):​c.1153C>T​(p.Arg385Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000513 in 152,132 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00051 (0 hom., cov: 28)
  • Exomes 𝑓: 0.00011 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: WASHC2A NM_001005751.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.171
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.046195626).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001005751.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WASHC2A	NM_001005751.3	MANE Select	c.1153C>T	p.Arg385Trp	missense	Exon 13 of 31	NP_001005751.1	Q641Q2-1
	WASHC2A	NM_001291398.2		c.1153C>T	p.Arg385Trp	missense	Exon 13 of 30	NP_001278327.1	Q641Q2-2
	WASHC2A	NM_001437388.1		c.1081C>T	p.Arg361Trp	missense	Exon 12 of 30	NP_001424317.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WASHC2A	ENST00000282633.10	TSL:1 MANE Select	c.1153C>T	p.Arg385Trp	missense	Exon 13 of 31	ENSP00000282633.5	Q641Q2-1
	WASHC2A	ENST00000351071.11	TSL:1	c.1153C>T	p.Arg385Trp	missense	Exon 13 of 30	ENSP00000344037.6	Q641Q2-2
	WASHC2A	ENST00000314664.12	TSL:1	c.1153C>T	p.Arg385Trp	missense	Exon 13 of 29	ENSP00000314417.7	E7ESD2

Frequencies

GnomAD3 genomes AF: 0.000480 AC: 73 AN: 152014 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.00121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000918

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000883

Gnomad OTH AF: 0.000958

GnomAD2 exomes AF: 0.000117 AC: 8 AN: 68376 AF XY: 0.0000892

Gnomad AFR exome AF: 0.000666

Gnomad AMR exome AF: 0.000190

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000108 AC: 157 AN: 1454522 Hom.: 0 Cov.: 30 AF XY: 0.000101 AC XY: 73 AN XY: 723782

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000781 AC: 26 AN: 33306

American (AMR) AF: 0.000269 AC: 12 AN: 44646

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26070

East Asian (EAS) AF: 0.0000757 AC: 3 AN: 39654

South Asian (SAS) AF: 0.0000814 AC: 7 AN: 86034

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4122

European-Non Finnish (NFE) AF: 0.0000858 AC: 95 AN: 1107262

Other (OTH) AF: 0.000233 AC: 14 AN: 60016

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000513 AC: 78 AN: 152132 Hom.: 0 Cov.: 28 AF XY: 0.000578 AC XY: 43 AN XY: 74384

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00132 AC: 55 AN: 41528

American (AMR) AF: 0.000917 AC: 14 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10580

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000883 AC: 6 AN: 67960

Other (OTH) AF: 0.000948 AC: 2 AN: 2110

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0000843 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.075	T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.026	N
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.046	T
MetaSVM	Benign	-0.96	T
PhyloP100		0.17
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.17
Sift	Benign	0.091	T
Sift4G	Uncertain	0.010	D
Polyphen		0.41	B
Vest4		0.15
MutPred		0.17		Gain of helix (P = 0.062)
MVP		0.043
ClinPred		0.032	T
GERP RS		1.7
Varity_R		0.079
gMVP		0.18
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.19		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1422696859; hg19: chr10-51853650;