rs1554883535

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr10-50093306-G-A
• chr10-50093306-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001005751.3(WASHC2A):​c.1042G>A​(p.Asp348Asn) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 16)
  • Exomes 𝑓: 0.000034 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: WASHC2A NM_001005751.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.86
• 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.23666152).

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.1042G>A	p.Asp348Asn	missense	Exon 12 of 31	NP_001005751.1	Q641Q2-1
	WASHC2A	NM_001291398.2		c.1042G>A	p.Asp348Asn	missense	Exon 12 of 30	NP_001278327.1	Q641Q2-2
	WASHC2A	NM_001437388.1		c.970G>A	p.Asp324Asn	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.1042G>A	p.Asp348Asn	missense	Exon 12 of 31	ENSP00000282633.5	Q641Q2-1
	WASHC2A	ENST00000351071.11	TSL:1	c.1042G>A	p.Asp348Asn	missense	Exon 12 of 30	ENSP00000344037.6	Q641Q2-2
	WASHC2A	ENST00000314664.12	TSL:1	c.1042G>A	p.Asp348Asn	missense	Exon 12 of 29	ENSP00000314417.7	E7ESD2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 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: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000163 AC: 1 AN: 61224 AF XY: 0.0000330

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: 0.000121

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000336 AC: 44 AN: 1309706 Hom.: 0 Cov.: 27 AF XY: 0.0000275 AC XY: 18 AN XY: 655444

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

African (AFR) AF: 0.0000610 AC: 2 AN: 32772

American (AMR) AF: 0.0000992 AC: 4 AN: 40328

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23186

East Asian (EAS) AF: 0.00 AC: 0 AN: 39584

South Asian (SAS) AF: 0.00 AC: 0 AN: 82652

European-Finnish (FIN) AF: 0.0000196 AC: 1 AN: 51046

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3656

European-Non Finnish (NFE) AF: 0.0000346 AC: 34 AN: 981636

Other (OTH) AF: 0.0000547 AC: 3 AN: 54846

⚠️ 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 Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 124192 Hom.: 0 Cov.: 16 AF XY: 0.00 AC XY: 0 AN XY: 59648

African (AFR) AF: 0.00 AC: 0 AN: 37406

American (AMR) AF: 0.00 AC: 0 AN: 10558

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2686

East Asian (EAS) AF: 0.00 AC: 0 AN: 4976

South Asian (SAS) AF: 0.00 AC: 0 AN: 3688

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 244

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 54640

Other (OTH) AF: 0.00 AC: 0 AN: 1590

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	Benign	0.13
BayesDel_addAF	Benign	-0.050	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.24	T
MetaSVM	Uncertain	-0.033	T
PhyloP100		5.9
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-4.2	D
REVEL	Uncertain	0.31
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.013	D
Polyphen		1.0	D
Vest4		0.27
MVP		0.24
ClinPred		0.90	D
GERP RS		4.5
Varity_R		0.43
gMVP		0.30
Mutation Taster		=87/13	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: rs1554883535; hg19: chr10-51853066;