ENST00000381163.7:c.19C>T

Variant names:

• chrX-2843009-C-T
• rs11797037
• ENST00000381163.7:c.19C>T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000381163.7(GYG2):​c.19C>T​(p.His7Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 480,920 control chromosomes in the GnomAD database, including 4,071 homozygotes. There are 26,438 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.13 (758 hom., 3947 hem., cov: 22)
  • Exomes 𝑓: 0.16 (3313 hom. 22491 hem.)
• Consequence: GYG2 ENST00000381163.7 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0180

Genes affected

GYG2 (HGNC:4700): (glycogenin 2) This gene encodes a member of the the glycogenin family. Glycogenin is a self-glucosylating protein involved in the initiation reactions of glycogen biosynthesis. A gene on chromosome 3 encodes the muscle glycogenin and this X-linked gene encodes the glycogenin mainly present in liver; both are involved in blood glucose homeostasis. This gene has a short version on chromosome Y, which is 3' truncated and can not make a functional protein. Multiple alternatively spliced transcript variants encoding different isoforms have been identified.[provided by RefSeq, May 2010]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0041974485).
• BP6: Variant X-2843009-C-T is Benign according to our data. Variant chrX-2843009-C-T is described in ClinVar as [Benign]. Clinvar id is 379981.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GYG2	NM_001079855.2	c.8-204C>T		intron_variant	Intron 2 of 10	ENST00000398806.8	NP_001073324.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GYG2	ENST00000398806.8	c.8-204C>T		intron_variant	Intron 2 of 10	1	NM_001079855.2	ENSP00000381786.3

Frequencies

GnomAD3 genomes AF: 0.128 AC: 14028 AN: 109663 Hom.: 758 Cov.: 22 AF XY: 0.123 AC XY: 3947 AN XY: 31999

Gnomad AFR AF: 0.0622

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.220

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.123

GnomAD3 exomes AF: 0.158 AC: 13437 AN: 85079 Hom.: 811 AF XY: 0.171 AC XY: 3944 AN XY: 23065

Gnomad AFR exome AF: 0.0646

Gnomad AMR exome AF: 0.125

Gnomad ASJ exome AF: 0.116

Gnomad EAS exome AF: 0.171

Gnomad SAS exome AF: 0.295

Gnomad FIN exome AF: 0.132

Gnomad NFE exome AF: 0.156

Gnomad OTH exome AF: 0.162

GnomAD4 exome AF: 0.164 AC: 60814 AN: 371202 Hom.: 3313 Cov.: 2 AF XY: 0.179 AC XY: 22491 AN XY: 125544

Gnomad4 AFR exome AF: 0.0634

Gnomad4 AMR exome AF: 0.124

Gnomad4 ASJ exome AF: 0.121

Gnomad4 EAS exome AF: 0.163

Gnomad4 SAS exome AF: 0.298

Gnomad4 FIN exome AF: 0.132

Gnomad4 NFE exome AF: 0.160

Gnomad4 OTH exome AF: 0.156

GnomAD4 genome AF: 0.128 AC: 14022 AN: 109718 Hom.: 758 Cov.: 22 AF XY: 0.123 AC XY: 3947 AN XY: 32064

Gnomad4 AFR AF: 0.0619

Gnomad4 AMR AF: 0.104

Gnomad4 ASJ AF: 0.116

Gnomad4 EAS AF: 0.166

Gnomad4 SAS AF: 0.291

Gnomad4 FIN AF: 0.116

Gnomad4 NFE AF: 0.160

Gnomad4 OTH AF: 0.127

Alfa AF: 0.137 Hom.: 1165

Bravo AF: 0.124

TwinsUK AF: 0.170 AC: 629

ALSPAC AF: 0.164 AC: 474

ExAC AF: 0.102 AC: 5515

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

Dec 28, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.86	T
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.4
DANN	Benign	0.87
DEOGEN2	Benign	0.0014	T;.;.
FATHMM_MKL	Benign	0.0018	N
LIST_S2	Benign	0.63	T;T;T
MetaRNN	Benign	0.0042	T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.8	L;L;.
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.26	N;.;.
REVEL	Benign	0.089
Sift	Pathogenic	0.0	D;.;.
Sift4G	Benign	0.16	T;T;.
Polyphen		0.62	P;.;.
Vest4		0.11
MPC		0.082
ClinPred		0.010	T
GERP RS		-0.51
Varity_R		0.16
gMVP		0.22

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

LitVar

Other links and lift over

dbSNP: rs11797037; hg19: chrX-2761050; COSMIC: COSV58549061;