11-124747591-G-T

Position:

• chr11-124747591-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014312.5(VSIG2):​c.928C>A​(p.Pro310Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000753 in 1,461,674 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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: 0.0000075 (0 hom.)
• Consequence: VSIG2 NM_014312.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.850

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.028603047).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VSIG2	NM_014312.5	c.928C>A	p.Pro310Thr	missense_variant	7/7	ENST00000326621.10	NP_055127.2
VSIG2	XM_047426685.1	c.562C>A	p.Pro188Thr	missense_variant	5/5		XP_047282641.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VSIG2	ENST00000326621.10	c.928C>A	p.Pro310Thr	missense_variant	7/7	1	NM_014312.5	ENSP00000318684.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000753 AC: 11 AN: 1461674 Hom.: 0 Cov.: 30 AF XY: 0.00000825 AC XY: 6 AN XY: 727146

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000719

Gnomad4 OTH exome AF: 0.0000331

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

Dec 13, 2022

The c.928C>A (p.P310T) alteration is located in exon 7 (coding exon 7) of the VSIG2 gene. This alteration results from a C to A substitution at nucleotide position 928, causing the proline (P) at amino acid position 310 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	0.064
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	0.60
DANN	Benign	0.73
DEOGEN2	Benign	0.0042	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.031	N
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.0088	T
MetaRNN	Benign	0.029	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.69	N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.18	N
REVEL	Benign	0.074
Sift	Benign	0.21	T
Sift4G	Benign	0.98	T
Polyphen		0.0	B
Vest4		0.15
MutPred		0.18		Gain of phosphorylation at P310 (P = 0.0478);
MVP		0.10
MPC		0.044
ClinPred		0.061	T
GERP RS		-6.0
Varity_R		0.049
gMVP		0.36

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: chr11-124617487;