12-108224776-C-G

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_014653.4(WSCD2):c.720C>G(p.Pro240=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00145 in 1,613,486 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0014 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0015 (6 hom.)
• Consequence: WSCD2 NM_014653.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.19

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 Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 12-108224776-C-G is Benign according to our data. Variant chr12-108224776-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2643264.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.19 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WSCD2	NM_014653.4	c.720C>G	p.Pro240=	synonymous_variant	5/9	ENST00000547525.6
LOC124903077	XR_007063583.1	n.182+9240G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WSCD2	ENST00000547525.6	c.720C>G	p.Pro240=	synonymous_variant	5/9	1	NM_014653.4	P1
WSCD2	ENST00000332082.8	c.720C>G	p.Pro240=	synonymous_variant	6/10	1		P1
WSCD2	ENST00000549903.1	c.720C>G	p.Pro240=	synonymous_variant	4/9	5
WSCD2	ENST00000551638.5	c.261C>G	p.Pro87=	synonymous_variant	4/5	4

Frequencies

GnomAD3 genomes AF: 0.00143 AC: 217 AN: 152232 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000289

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.00150

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00197

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00137 AC: 340 AN: 248668 Hom.: 1 AF XY: 0.00135 AC XY: 182 AN XY: 134992

Gnomad AFR exome AF: 0.000323

Gnomad AMR exome AF: 0.00200

Gnomad ASJ exome AF: 0.000596

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.000144

Gnomad NFE exome AF: 0.00218

Gnomad OTH exome AF: 0.000992

GnomAD4 exome AF: 0.00146 AC: 2129 AN: 1461136 Hom.: 6 Cov.: 30 AF XY: 0.00148 AC XY: 1074 AN XY: 726906

Gnomad4 AFR exome AF: 0.0000896

Gnomad4 AMR exome AF: 0.00224

Gnomad4 ASJ exome AF: 0.000880

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000151

Gnomad4 FIN exome AF: 0.000133

Gnomad4 NFE exome AF: 0.00168

Gnomad4 OTH exome AF: 0.00159

GnomAD4 genome AF: 0.00142 AC: 217 AN: 152350 Hom.: 0 Cov.: 33 AF XY: 0.00133 AC XY: 99 AN XY: 74506

Gnomad4 AFR AF: 0.000289

Gnomad4 AMR AF: 0.00150

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00197

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00128 Hom.: 0

Bravo AF: 0.00159

EpiCase AF: 0.00305

EpiControl AF: 0.00249

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

WSCD2: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
Cadd	Benign	0.37
Dann	Benign	0.53

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: rs199888315; hg19: chr12-108618553;