12-108210251-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014653.4(WSCD2):c.628G>A(p.Ala210Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000188 in 1,438,704 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000019 (0 hom.)
• Consequence: WSCD2 NM_014653.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.28

Genes affected

WSCD2 (HGNC:29117): (WSC domain containing 2) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

LOC124903077 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12125844).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WSCD2	NM_014653.4	c.628G>A	p.Ala210Thr	missense_variant	4/9	ENST00000547525.6
LOC124903077	XR_007063583.1	n.183-19232C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WSCD2	ENST00000547525.6	c.628G>A	p.Ala210Thr	missense_variant	4/9	1	NM_014653.4	P1
WSCD2	ENST00000332082.8	c.628G>A	p.Ala210Thr	missense_variant	5/10	1		P1
WSCD2	ENST00000549903.1	c.628G>A	p.Ala210Thr	missense_variant	3/9	5
WSCD2	ENST00000551638.5	c.169G>A	p.Ala57Thr	missense_variant	3/5	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000386 AC: 8 AN: 207136 Hom.: 0 AF XY: 0.0000351 AC XY: 4 AN XY: 113882

Gnomad AFR exome AF: 0.0000814

Gnomad AMR exome AF: 0.0000614

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000687

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000353

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000188 AC: 27 AN: 1438704 Hom.: 0 Cov.: 32 AF XY: 0.0000168 AC XY: 12 AN XY: 714444

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000919

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000513

Gnomad4 SAS exome AF: 0.0000469

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000146

Gnomad4 OTH exome AF: 0.0000169

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000113

ExAC AF: 0.0000521 AC: 6

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Marfanoid habitus and intellectual disability Uncertain:1

Uncertain significance, criteria provided, single submitter

research

Equipe Genetique des Anomalies du Developpement, Université de Bourgogne

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
Cadd	Benign	22
Dann	Uncertain	1.0
DEOGEN2	Benign	0.0039	T;.;T;.
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.060
FATHMM_MKL	Uncertain	0.91	D
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.12	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L;.;L;L
MutationTaster	Benign	0.75	N;N;N;N
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.58	N;N;N;N
REVEL	Benign	0.016
Sift	Benign	0.14	T;T;T;T
Sift4G	Benign	0.40	T;T;T;T
Polyphen		0.22	B;.;B;.
Vest4		0.40
MutPred		0.42		Gain of catalytic residue at N211 (P = 0);.;Gain of catalytic residue at N211 (P = 0);Gain of catalytic residue at N211 (P = 0);
MVP		0.11
MPC		0.36
ClinPred		0.029	T
GERP RS		4.2
Varity_R		0.051
gMVP		0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs771199825; hg19: chr12-108604028; COSMIC: COSV54585175;