17-6080663-C-A

Position:

• chr17-6080663-C-A

Variant summary

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

The NM_015253.2(WSCD1):​c.5C>A​(p.Ala2Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. A2T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: WSCD1 NM_015253.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.98

Genes affected

WSCD1 (HGNC:29060): (WSC domain containing 1) Predicted to enable sulfotransferase activity. Predicted to be located in membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WSCD1	NM_015253.2	c.5C>A	p.Ala2Asp	missense_variant	2/9	ENST00000317744.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WSCD1	ENST00000317744.10	c.5C>A	p.Ala2Asp	missense_variant	2/9	1	NM_015253.2	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 26, 2022

The c.5C>A (p.A2D) alteration is located in exon 2 (coding exon 1) of the WSCD1 gene. This alteration results from a C to A substitution at nucleotide position 5, causing the alanine (A) at amino acid position 2 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.77
BayesDel_addAF	Pathogenic	0.33	D
BayesDel_noAF	Pathogenic	0.24
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	.;T;T;T;T;T;.;.
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.73	T;.;T;.;.;T;T;T
M_CAP	Uncertain	0.19	D
MetaRNN	Uncertain	0.73	D;D;D;D;D;D;D;D
MetaSVM	Uncertain	0.20	D
MutationAssessor	Uncertain	2.2	.;M;.;M;M;M;.;.
MutationTaster	Benign	0.99	D;D;D;D;D
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-3.4	.;.;.;D;.;D;.;.
REVEL	Pathogenic	0.66
Sift	Uncertain	0.0010	.;.;.;D;.;D;.;.
Sift4G	Pathogenic	0.0	D;D;D;D;D;D;D;D
Polyphen		0.98	.;D;.;D;D;D;.;.
Vest4		0.90, 0.90
MutPred		0.28		Loss of catalytic residue at A2 (P = 0.0137);Loss of catalytic residue at A2 (P = 0.0137);Loss of catalytic residue at A2 (P = 0.0137);Loss of catalytic residue at A2 (P = 0.0137);Loss of catalytic residue at A2 (P = 0.0137);Loss of catalytic residue at A2 (P = 0.0137);Loss of catalytic residue at A2 (P = 0.0137);Loss of catalytic residue at A2 (P = 0.0137);
MVP		0.83
MPC		1.1
ClinPred		0.97	D
GERP RS		3.8
Varity_R		0.55
gMVP		0.77

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: rs1909172450; hg19: chr17-5983983;