chr7-54542774-C-A

Position:

• chr7-54542774-C-A

Variant summary

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

The NM_001301009.2(VSTM2A):​c.44C>A​(p.Ser15Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,536 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: VSTM2A NM_001301009.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.88

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 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
VSTM2A	NM_001301009.2	c.44C>A	p.Ser15Tyr	missense_variant	1/5	ENST00000402613.4	NP_001287938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VSTM2A	ENST00000402613.4	c.44C>A	p.Ser15Tyr	missense_variant	1/5	2	NM_001301009.2	ENSP00000384103	A1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461536 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727040

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000447

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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

Feb 26, 2024

The c.44C>A (p.S15Y) alteration is located in exon 1 (coding exon 1) of the VSTM2A gene. This alteration results from a C to A substitution at nucleotide position 44, causing the serine (S) at amino acid position 15 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	0.26
BayesDel_addAF	Benign	-0.0083	T
BayesDel_noAF	Benign	-0.25
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	.;T;.;T
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.92	D;D;D;D
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.50	T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.7	L;L;.;.
MutationTaster	Benign	0.74	N;N;N;N;N
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-1.5	N;N;N;N
REVEL	Benign	0.19
Sift	Benign	0.069	T;T;T;T
Sift4G	Benign	0.084	T;T;T;T
Polyphen		0.92	P;P;P;.
Vest4		0.60
MutPred		0.35		Gain of sheet (P = 1e-04);Gain of sheet (P = 1e-04);Gain of sheet (P = 1e-04);Gain of sheet (P = 1e-04);
MVP		0.30
MPC		0.59
ClinPred		0.87	D
GERP RS		4.0
Varity_R		0.18
gMVP		0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr7-54610467;