2-1083536-C-A

Position:

• chr2-1083536-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_018968.4(SNTG2):​c.91C>A​(p.Leu31Met) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SNTG2 NM_018968.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.314

Genes affected

SNTG2 (HGNC:13741): (syntrophin gamma 2) This gene encodes a protein belonging to the syntrophin family. Syntrophins are cytoplasmic peripheral membrane proteins that bind to components of mechanosenstive sodium channels and the extreme carboxy-terminal domain of dystrophin and dystrophin-related proteins. The PDZ domain of this protein product interacts with a protein component of a mechanosensitive sodium channel that affects channel gating. Absence or reduction of this protein product has been associated with Duchenne muscular dystrophy. There is evidence of alternative splicing yet the full-length nature of these variants has not been described. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30016994).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNTG2	NM_018968.4	c.91C>A	p.Leu31Met	missense_variant	2/17	ENST00000308624.10	NP_061841.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNTG2	ENST00000308624.10	c.91C>A	p.Leu31Met	missense_variant	2/17	1	NM_018968.4	ENSP00000311837	P1
SNTG2	ENST00000407292.1	c.91C>A	p.Leu31Met	missense_variant	2/11	1		ENSP00000385020
SNTG2	ENST00000450962.5	c.91C>A	p.Leu31Met	missense_variant, NMD_transcript_variant	2/8	5		ENSP00000401997
SNTG2	ENST00000452177.5	c.91C>A	p.Leu31Met	missense_variant, NMD_transcript_variant	2/8	2		ENSP00000412249

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

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

Oct 04, 2022

The c.91C>A (p.L31M) alteration is located in exon 2 (coding exon 2) of the SNTG2 gene. This alteration results from a C to A substitution at nucleotide position 91, causing the leucine (L) at amino acid position 31 to be replaced by a methionine (M). 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	0.11
BayesDel_addAF	Benign	-0.016	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	11
DANN	Uncertain	0.98
DEOGEN2	Benign	0.048	T;.
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.073	N
LIST_S2	Benign	0.81	T;T
M_CAP	Uncertain	0.085	D
MetaRNN	Benign	0.30	T;T
MetaSVM	Uncertain	-0.25	T
MutationAssessor	Uncertain	2.4	M;M
MutationTaster	Benign	1.0	N;N
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.72	N;N
REVEL	Benign	0.21
Sift	Benign	0.11	T;T
Sift4G	Benign	0.16	T;D
Polyphen		0.99	D;D
Vest4		0.40
MutPred		0.34		Loss of sheet (P = 0.0357);Loss of sheet (P = 0.0357);
MVP		0.31
MPC		0.43
ClinPred		0.66	D
GERP RS		-1.7
Varity_R		0.070
gMVP		0.37

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: chr2-1079222;