10-50093295-C-G

Variant names:

• chr10-50093295-C-G
• rs1443043282
• NM_001005751.3:c.1031C>G

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001005751.3(WASHC2A):​c.1031C>G​(p.Pro344Arg) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P344L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 16)
  • Exomes 𝑓: 0.00011 (7 hom.)
  • Failed GnomAD Quality Control
• Consequence: WASHC2A NM_001005751.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.03
• 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 -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.34781128).

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.1031C>G	p.Pro344Arg	missense	Exon 12 of 31	NP_001005751.1	Q641Q2-1
	WASHC2A	NM_001291398.2		c.1031C>G	p.Pro344Arg	missense	Exon 12 of 30	NP_001278327.1	Q641Q2-2
	WASHC2A	NM_001437388.1		c.959C>G	p.Pro320Arg	missense	Exon 11 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.1031C>G	p.Pro344Arg	missense	Exon 12 of 31	ENSP00000282633.5	Q641Q2-1
	WASHC2A	ENST00000351071.11	TSL:1	c.1031C>G	p.Pro344Arg	missense	Exon 12 of 30	ENSP00000344037.6	Q641Q2-2
	WASHC2A	ENST00000314664.12	TSL:1	c.1031C>G	p.Pro344Arg	missense	Exon 12 of 29	ENSP00000314417.7	E7ESD2

Frequencies

GnomAD3 genomes AF: 0.000116 AC: 14 AN: 120792 Hom.: 0 Cov.: 16

Gnomad AFR AF: 0.0000547

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000283

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000187

Gnomad OTH AF: 0.000656

GnomAD2 exomes AF: 0.0000342 AC: 2 AN: 58478 AF XY: 0.0000687

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000506

Gnomad OTH exome AF: 0.000550

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000110 AC: 138 AN: 1251214 Hom.: 7 Cov.: 21 AF XY: 0.000132 AC XY: 83 AN XY: 628930

African (AFR) AF: 0.0000629 AC: 2 AN: 31790

American (AMR) AF: 0.0000497 AC: 2 AN: 40236

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22496

East Asian (EAS) AF: 0.00 AC: 0 AN: 39498

South Asian (SAS) AF: 0.0000245 AC: 2 AN: 81580

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50818

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3522

European-Non Finnish (NFE) AF: 0.000131 AC: 122 AN: 928394

Other (OTH) AF: 0.000189 AC: 10 AN: 52880

GnomAD4 genome AF: 0.000108 AC: 13 AN: 120872 Hom.: 0 Cov.: 16 AF XY: 0.000104 AC XY: 6 AN XY: 57818

African (AFR) AF: 0.0000546 AC: 2 AN: 36644

American (AMR) AF: 0.00 AC: 0 AN: 10172

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2646

East Asian (EAS) AF: 0.00 AC: 0 AN: 4878

South Asian (SAS) AF: 0.000283 AC: 1 AN: 3532

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7128

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 208

European-Non Finnish (NFE) AF: 0.000169 AC: 9 AN: 53332

Other (OTH) AF: 0.000650 AC: 1 AN: 1538

Alfa AF: 0.00 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	Uncertain	0.53
BayesDel_addAF	Benign	-0.038	T
BayesDel_noAF	Benign	-0.12
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.37	T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.35	T
MetaSVM	Uncertain	-0.053	T
PhyloP100		6.0
PrimateAI	Pathogenic	0.79	T
PROVEAN	Pathogenic	-7.4	D
REVEL	Uncertain	0.35
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.48
MutPred		0.28		Gain of solvent accessibility (P = 0.0026)
MVP		0.18
ClinPred		0.91	D
GERP RS		4.5
Varity_R		0.75
gMVP		0.34
Mutation Taster		=85/15	polymorphism

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

Other links and lift over

dbSNP: rs1443043282; hg19: chr10-51853055;