chr7-54544775-G-T

Position:

• chr7-54544775-G-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001301009.2(VSTM2A):​c.233G>T​(p.Gly78Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: VSTM2A NM_001301009.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.979

Genes affected

VSTM2A (HGNC:28499): (V-set and transmembrane domain containing 2A) Predicted to enable identical protein binding activity. Involved in several processes, including positive regulation of brown fat cell differentiation; positive regulation of lipid storage; and positive regulation of white fat cell proliferation. Predicted to be located in extracellular region. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.036631882).
• BP6: Variant 7-54544775-G-T is Benign according to our data. Variant chr7-54544775-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 3468634.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VSTM2A	NM_001301009.2	c.233G>T	p.Gly78Val	missense_variant	2/5	ENST00000402613.4	NP_001287938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VSTM2A	ENST00000402613.4	c.233G>T	p.Gly78Val	missense_variant	2/5	2	NM_001301009.2	ENSP00000384103.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 03, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.053
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	8.3
DANN	Benign	0.80
DEOGEN2	Benign	0.010	.;T;.;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.71	T;T;T;T
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.037	T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-1.2	N;N;.;.
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.30	N;N;N;N
REVEL	Benign	0.038
Sift	Benign	0.57	T;T;T;T
Sift4G	Benign	0.47	T;T;T;T
Polyphen		0.0010	B;B;B;.
Vest4		0.10
MutPred		0.43		Loss of sheet (P = 0.0011);Loss of sheet (P = 0.0011);Loss of sheet (P = 0.0011);Loss of sheet (P = 0.0011);
MVP		0.048
MPC		0.28
ClinPred		0.043	T
GERP RS		-1.6
Varity_R		0.044
gMVP		0.25

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: chr7-54612468;