chr2-951039-C-G

Position:

• chr2-951039-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018968.4(SNTG2):​c.43C>G​(p.Arg15Gly) 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. 13/21 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)
• Consequence: SNTG2 NM_018968.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.113

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]

SNTG2-AS1 (HGNC:54058): (SNTG2 antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10514042).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNTG2	NM_018968.4	c.43C>G	p.Arg15Gly	missense_variant	1/17	ENST00000308624.10	NP_061841.2
SNTG2-AS1	NR_136151.1	n.108+246G>C		intron_variant, non_coding_transcript_variant
SNTG2	XM_047444795.1	c.43C>G	p.Arg15Gly	missense_variant	1/13		XP_047300751.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNTG2	ENST00000308624.10	c.43C>G	p.Arg15Gly	missense_variant	1/17	1	NM_018968.4	ENSP00000311837	P1
SNTG2-AS1	ENST00000684906.1	n.218+246G>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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 01, 2022

The c.43C>G (p.R15G) alteration is located in exon 1 (coding exon 1) of the SNTG2 gene. This alteration results from a C to G substitution at nucleotide position 43, causing the arginine (R) at amino acid position 15 to be replaced by a glycine (G). 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	0.12
BayesDel_addAF	Benign	-0.078	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	17
DANN	Benign	0.93
DEOGEN2	Benign	0.011	T;.
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.53	T;T
M_CAP	Uncertain	0.17	D
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.4	L;L
MutationTaster	Benign	1.0	N;N
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.066
Sift	Benign	0.046	D;D
Sift4G	Benign	0.30	T;T
Polyphen		0.36	B;B
Vest4		0.20
MutPred		0.47		Loss of MoRF binding (P = 0.0578);Loss of MoRF binding (P = 0.0578);
MVP		0.25
MPC		0.19
ClinPred		0.093	T
GERP RS		1.2
Varity_R		0.16
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: chr2-946725;