12-108195870-G-C

Variant names:

• chr12-108195870-G-C
• rs751049061
• NM_014653.4:c.38G>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_014653.4(WSCD2):​c.38G>C​(p.Arg13Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. R13H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: WSCD2 NM_014653.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.54
• Publications: 0 publications found

Genes affected

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

ENSG00000307044 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.826

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014653.4. 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
	WSCD2	NM_014653.4	MANE Select	c.38G>C	p.Arg13Pro	missense	Exon 2 of 9	NP_055468.2
	WSCD2	NM_001304447.2		c.38G>C	p.Arg13Pro	missense	Exon 3 of 10	NP_001291376.1	Q2TBF2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WSCD2	ENST00000547525.6	TSL:1 MANE Select	c.38G>C	p.Arg13Pro	missense	Exon 2 of 9	ENSP00000448047.1	Q2TBF2-1
	WSCD2	ENST00000332082.8	TSL:1	c.38G>C	p.Arg13Pro	missense	Exon 3 of 10	ENSP00000331933.4	Q2TBF2-1
	WSCD2	ENST00000549903.1	TSL:5	c.38G>C	p.Arg13Pro	missense	Exon 1 of 9	ENSP00000447272.1	Q2TBF2-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.64
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	T
Eigen	Pathogenic	0.91
Eigen_PC	Pathogenic	0.91
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.038	D
MetaRNN	Pathogenic	0.83	D
MetaSVM	Benign	-0.57	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		9.5
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-4.3	D
REVEL	Pathogenic	0.66
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.011	D
Polyphen		1.0	D
Vest4		0.81
MutPred		0.55		Gain of catalytic residue at K15 (P = 0)
MVP		0.60
MPC		1.4
ClinPred		0.99	D
GERP RS		5.7
PromoterAI		-0.21	Neutral
Varity_R		0.85
gMVP		0.74
Mutation Taster		=45/55	disease causing

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: rs751049061; hg19: chr12-108589647;