chr2-1083594-A-C

Position:

• chr2-1083594-A-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_018968.4(SNTG2):​c.149A>C​(p.Glu50Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0104 in 1,613,752 control chromosomes in the GnomAD database, including 135 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0088 (7 hom., cov: 33)
  • Exomes 𝑓: 0.011 (128 hom.)
• Consequence: SNTG2 NM_018968.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 7.47

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 Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0050479174).
• BP6: Variant 2-1083594-A-C is Benign according to our data. Variant chr2-1083594-A-C is described in ClinVar as [Benign]. Clinvar id is 780020.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNTG2	NM_018968.4	c.149A>C	p.Glu50Ala	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.149A>C	p.Glu50Ala	missense_variant	2/17	1	NM_018968.4	ENSP00000311837	P1
SNTG2	ENST00000407292.1	c.149A>C	p.Glu50Ala	missense_variant	2/11	1		ENSP00000385020
SNTG2	ENST00000450962.5	c.149A>C	p.Glu50Ala	missense_variant, NMD_transcript_variant	2/8	5		ENSP00000401997
SNTG2	ENST00000452177.5	c.149A>C	p.Glu50Ala	missense_variant, NMD_transcript_variant	2/8	2		ENSP00000412249

Frequencies

GnomAD3 genomes AF: 0.00878 AC: 1336 AN: 152182 Hom.: 7 Cov.: 33

Gnomad AFR AF: 0.00157

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.00766

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.0376

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0103

Gnomad OTH AF: 0.00861

GnomAD3 exomes AF: 0.00958 AC: 2386 AN: 249058 Hom.: 29 AF XY: 0.00959 AC XY: 1296 AN XY: 135098

Gnomad AFR exome AF: 0.00149

Gnomad AMR exome AF: 0.00472

Gnomad ASJ exome AF: 0.00507

Gnomad EAS exome AF: 0.0000556

Gnomad SAS exome AF: 0.00173

Gnomad FIN exome AF: 0.0332

Gnomad NFE exome AF: 0.0117

Gnomad OTH exome AF: 0.0102

GnomAD4 exome AF: 0.0105 AC: 15406 AN: 1461452 Hom.: 128 Cov.: 34 AF XY: 0.0103 AC XY: 7484 AN XY: 727016

Gnomad4 AFR exome AF: 0.00143

Gnomad4 AMR exome AF: 0.00476

Gnomad4 ASJ exome AF: 0.00379

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00155

Gnomad4 FIN exome AF: 0.0334

Gnomad4 NFE exome AF: 0.0113

Gnomad4 OTH exome AF: 0.00855

GnomAD4 genome AF: 0.00877 AC: 1336 AN: 152300 Hom.: 7 Cov.: 33 AF XY: 0.00955 AC XY: 711 AN XY: 74466

Gnomad4 AFR AF: 0.00156

Gnomad4 AMR AF: 0.00765

Gnomad4 ASJ AF: 0.00317

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.0376

Gnomad4 NFE AF: 0.0103

Gnomad4 OTH AF: 0.00852

Alfa AF: 0.00959 Hom.: 13

Bravo AF: 0.00691

TwinsUK AF: 0.0146 AC: 54

ALSPAC AF: 0.0127 AC: 49

ESP6500AA AF: 0.00174 AC: 7

ESP6500EA AF: 0.0114 AC: 95

ExAC AF: 0.00949 AC: 1148

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.0116

EpiControl AF: 0.00996

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 15, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T;.
Eigen	Uncertain	0.28
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.96	D;D
MetaRNN	Benign	0.0050	T;T
MetaSVM	Benign	-0.65	T
MutationAssessor	Uncertain	2.3	M;M
MutationTaster	Benign	1.0	D;N
PrimateAI	Benign	0.42	T
PROVEAN	Pathogenic	-4.7	D;N
REVEL	Uncertain	0.32
Sift	Uncertain	0.0060	D;D
Sift4G	Uncertain	0.012	D;D
Polyphen		0.95	P;D
Vest4		0.50
MVP		0.52
MPC		0.40
ClinPred		0.041	T
GERP RS		4.2
Varity_R		0.48
gMVP		0.55

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

LitVar

Other links and lift over

dbSNP: rs142024310; hg19: chr2-1079280;