10-50093306-G-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2624301).

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>T	p.Asp348Tyr	missense	Exon 12 of 31	NP_001005751.1	Q641Q2-1
	WASHC2A	NM_001291398.2		c.1042G>T	p.Asp348Tyr	missense	Exon 12 of 30	NP_001278327.1	Q641Q2-2
	WASHC2A	NM_001437388.1		c.970G>T	p.Asp324Tyr	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>T	p.Asp348Tyr	missense	Exon 12 of 31	ENSP00000282633.5	Q641Q2-1
	WASHC2A	ENST00000351071.11	TSL:1	c.1042G>T	p.Asp348Tyr	missense	Exon 12 of 30	ENSP00000344037.6	Q641Q2-2
	WASHC2A	ENST00000314664.12	TSL:1	c.1042G>T	p.Asp348Tyr	missense	Exon 12 of 29	ENSP00000314417.7	E7ESD2

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

African (AFR) AF: 0.00 AC: 0 AN: 32772

American (AMR) AF: 0.00 AC: 0 AN: 40330

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39586

South Asian (SAS) AF: 0.0000363 AC: 3 AN: 82652

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51046

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 981672

Other (OTH) AF: 0.00 AC: 0 AN: 54846

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

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

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: 0.000271 AC: 1 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

⚠️ 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: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Pathogenic	0.97	D
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.26	T
MetaSVM	Uncertain	-0.012	T
PhyloP100		5.9
PrimateAI	Uncertain	0.77	T
PROVEAN	Pathogenic	-7.6	D
REVEL	Uncertain	0.35
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.42
MutPred		0.26		Loss of loop (P = 0.0374)
MVP		0.068
ClinPred		1.0	D
GERP RS		4.5
Varity_R		0.86
gMVP		0.44
Mutation Taster		=83/17	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;