11-124748670-G-T

Variant names:

• chr11-124748670-G-T
• NM_014312.5:c.680C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_014312.5(VSIG2):​c.680C>A​(p.Ser227Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: VSIG2 NM_014312.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.83
• Publications: 0 publications found

Genes affected

VSIG2 (HGNC:17149): (V-set and immunoglobulin domain containing 2) Predicted to be located in membrane. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VSIG2	NM_014312.5	c.680C>A	p.Ser227Tyr	missense_variant	Exon 5 of 7	ENST00000326621.10	NP_055127.2
VSIG2	NM_001329920.2	c.680C>A	p.Ser227Tyr	missense_variant	Exon 5 of 6		NP_001316849.1
VSIG2	XM_047426685.1	c.314C>A	p.Ser105Tyr	missense_variant	Exon 3 of 5		XP_047282641.1
VSIG2	XM_047426684.1	c.*90C>A		downstream_gene_variant			XP_047282640.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VSIG2	ENST00000326621.10	c.680C>A	p.Ser227Tyr	missense_variant	Exon 5 of 7	1	NM_014312.5	ENSP00000318684.5
VSIG2	ENST00000403470.1	c.680C>A	p.Ser227Tyr	missense_variant	Exon 5 of 6	2		ENSP00000385013.1

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

Aug 04, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.680C>A (p.S227Y) alteration is located in exon 5 (coding exon 5) of the VSIG2 gene. This alteration results from a C to A substitution at nucleotide position 680, causing the serine (S) at amino acid position 227 to be replaced by a tyrosine (Y). 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	Benign	0.16
BayesDel_addAF	Uncertain	0.024	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T;.
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.70	T;T
M_CAP	Benign	0.034	D
MetaRNN	Uncertain	0.57	D;D
MetaSVM	Benign	-0.52	T
MutationAssessor	Benign	1.8	L;L
PhyloP100		1.8
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-3.6	D;D
REVEL	Benign	0.23
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.050	T;D
Polyphen		0.85	P;.
Vest4		0.58
MutPred		0.47		Loss of disorder (P = 0.0252);Loss of disorder (P = 0.0252);
MVP		0.63
MPC		0.19
ClinPred		0.99	D
GERP RS		3.5
Varity_R		0.33
gMVP		0.60
Mutation Taster		=88/12	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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

hg19: chr11-124618566;