chr11-124750762-G-T

Position:

• chr11-124750762-G-T

Variant summary

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

The NM_014312.5(VSIG2):​c.379C>A​(p.Pro127Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,461,416 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: VSIG2 NM_014312.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.70

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

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	Protein	UniProt
VSIG2	NM_014312.5	c.379C>A	p.Pro127Thr	missense_variant	3/7	ENST00000326621.10	NP_055127.2
VSIG2	NM_001329920.2	c.379C>A	p.Pro127Thr	missense_variant	3/6		NP_001316849.1
VSIG2	XM_047426684.1	c.379C>A	p.Pro127Thr	missense_variant	3/5		XP_047282640.1
VSIG2	XM_047426685.1	c.62-896C>A		intron_variant			XP_047282641.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VSIG2	ENST00000326621.10	c.379C>A	p.Pro127Thr	missense_variant	3/7	1	NM_014312.5	ENSP00000318684.5
VSIG2	ENST00000403470.1	c.379C>A	p.Pro127Thr	missense_variant	3/6	2		ENSP00000385013.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461416 Hom.: 0 Cov.: 32 AF XY: 0.00000825 AC XY: 6 AN XY: 726980

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000813

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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

Nov 22, 2022

The c.379C>A (p.P127T) alteration is located in exon 3 (coding exon 3) of the VSIG2 gene. This alteration results from a C to A substitution at nucleotide position 379, causing the proline (P) at amino acid position 127 to be replaced by a threonine (T). 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	0.31
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T;.
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.76	T;T
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.67	D;D
MetaSVM	Benign	-0.85	T
MutationAssessor	Pathogenic	2.9	M;M
PrimateAI	Uncertain	0.54	T
PROVEAN	Pathogenic	-7.3	D;D
REVEL	Benign	0.23
Sift	Uncertain	0.021	D;D
Sift4G	Benign	0.14	T;T
Polyphen		1.0	D;.
Vest4		0.60
MutPred		0.51		Loss of catalytic residue at P126 (P = 0.0393);Loss of catalytic residue at P126 (P = 0.0393);
MVP		0.36
MPC		0.30
ClinPred		1.0	D
GERP RS		5.1
Varity_R		0.59
gMVP		0.47

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-124620658;