2-1083646-G-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The ENST00000308624.10(SNTG2):ā€‹c.201G>Cā€‹(p.Gln67His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000477 in 1,613,750 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (ā˜…).

Frequency

Genomes: š‘“ 0.00020 ( 0 hom., cov: 33)
Exomes š‘“: 0.000032 ( 0 hom. )

Consequence

SNTG2
ENST00000308624.10 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.398
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.01988557).
BP6
Variant 2-1083646-G-C is Benign according to our data. Variant chr2-1083646-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2360735.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SNTG2NM_018968.4 linkuse as main transcriptc.201G>C p.Gln67His missense_variant 2/17 ENST00000308624.10 NP_061841.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SNTG2ENST00000308624.10 linkuse as main transcriptc.201G>C p.Gln67His missense_variant 2/171 NM_018968.4 ENSP00000311837 P1Q9NY99-1
SNTG2ENST00000407292.1 linkuse as main transcriptc.201G>C p.Gln67His missense_variant 2/111 ENSP00000385020 Q9NY99-2
SNTG2ENST00000450962.5 linkuse as main transcriptc.201G>C p.Gln67His missense_variant, NMD_transcript_variant 2/85 ENSP00000401997
SNTG2ENST00000452177.5 linkuse as main transcriptc.201G>C p.Gln67His missense_variant, NMD_transcript_variant 2/82 ENSP00000412249

Frequencies

GnomAD3 genomes
AF:
0.000197
AC:
30
AN:
152212
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00164
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000482
AC:
12
AN:
248944
Hom.:
0
AF XY:
0.0000518
AC XY:
7
AN XY:
135044
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000203
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000444
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000322
AC:
47
AN:
1461420
Hom.:
0
Cov.:
33
AF XY:
0.0000303
AC XY:
22
AN XY:
726996
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.000179
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:
0.0000279
Gnomad4 OTH exome
AF:
0.0000994
GnomAD4 genome
AF:
0.000197
AC:
30
AN:
152330
Hom.:
0
Cov.:
33
AF XY:
0.000215
AC XY:
16
AN XY:
74508
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00163
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000675
Hom.:
0
Bravo
AF:
0.000344
ExAC
AF:
0.0000414
AC:
5
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsJul 06, 2021This 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
0.085
BayesDel_addAF
Benign
-0.52
T
BayesDel_noAF
Benign
-0.71
CADD
Benign
0.28
DANN
Benign
0.26
DEOGEN2
Benign
0.0050
T;.
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.016
N
LIST_S2
Benign
0.39
T;T
M_CAP
Benign
0.0088
T
MetaRNN
Benign
0.020
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.26
N;N
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.40
T
PROVEAN
Benign
-0.050
N;N
REVEL
Benign
0.0090
Sift
Benign
0.54
T;T
Sift4G
Benign
0.35
T;T
Polyphen
0.0
B;B
Vest4
0.053
MutPred
0.35
Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);
MVP
0.067
MPC
0.093
ClinPred
0.090
T
GERP RS
-1.6
Varity_R
0.034
gMVP
0.31

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs558071831; hg19: chr2-1079332; API