7-44065206-C-T

Position:

chr7-44065206-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000290.4(PGAM2):c.324G>A(p.Gly108Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00497 in 1,614,048 control chromosomes in the GnomAD database, including 368 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.027 ( 195 hom., cov: 33)

Exomes 𝑓: 0.0027 ( 173 hom. )

Consequence

PGAM2
NM_000290.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -3.64

Variant links:

Genes affected

PGAM2 (HGNC:8889): (phosphoglycerate mutase 2) Phosphoglycerate mutase (PGAM) catalyzes the reversible reaction of 3-phosphoglycerate (3-PGA) to 2-phosphoglycerate (2-PGA) in the glycolytic pathway. The PGAM is a dimeric enzyme containing, in different tissues, different proportions of a slow-migrating muscle (MM) isozyme, a fast-migrating brain (BB) isozyme, and a hybrid form (MB). This gene encodes muscle-specific PGAM subunit. Mutations in this gene cause muscle phosphoglycerate mutase eficiency, also known as glycogen storage disease X. [provided by RefSeq, Sep 2009]

PGAM2 links:

DBNL (HGNC:2696): (drebrin like) Enables cadherin binding activity. Predicted to be involved in several processes, including Rac protein signal transduction; nervous system development; and podosome assembly. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

DBNL links:

ENSG00000239775 (HGNC:):

ENSG00000239775 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 7-44065206-C-T is Benign according to our data. Variant chr7-44065206-C-T is described in ClinVar as [Benign]. Clinvar id is 360277.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.64 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0926 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PGAM2	NM_000290.4 linkuse as main transcript	c.324G>A	p.Gly108Gly	synonymous_variant	1/3	ENST00000297283.4	NP_000281.2	P15259
DBNL	NM_001014436.3 linkuse as main transcript	c.*4290C>T		3_prime_UTR_variant	13/13	ENST00000448521.6	NP_001014436.1	Q9UJU6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PGAM2	ENST00000297283.4 linkuse as main transcript	c.324G>A	p.Gly108Gly	synonymous_variant	1/3	1	NM_000290.4	ENSP00000297283.3		P15259
DBNL	ENST00000448521.6 linkuse as main transcript	c.*4290C>T		3_prime_UTR_variant	13/13	1	NM_001014436.3	ENSP00000411701.1		Q9UJU6-1

Frequencies

GnomAD3 genomes

AF:

0.0271

AC:

4118

AN:

152162

Hom.:

194

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0951

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00746

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000323

Gnomad OTH

AF:

0.0191

GnomAD3 exomes

AF:

0.00711

AC:

1786

AN:

251298

Hom.:

AF XY:

0.00508

AC XY:

690

AN XY:

135862

show subpopulations

Gnomad AFR exome

AF:

0.0990

Gnomad AMR exome

AF:

0.00411

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000123

Gnomad OTH exome

AF:

0.00244

GnomAD4 exome

AF:

0.00266

AC:

3891

AN:

1461768

Hom.:

173

Cov.:

AF XY:

0.00220

AC XY:

1603

AN XY:

727204

show subpopulations

Gnomad4 AFR exome

AF:

0.0941

Gnomad4 AMR exome

AF:

0.00474

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000139

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.000136

Gnomad4 OTH exome

AF:

0.00580

GnomAD4 genome

AF:

0.0271

AC:

4128

AN:

152280

Hom.:

195

Cov.:

AF XY:

0.0257

AC XY:

1916

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.0951

Gnomad4 AMR

AF:

0.00745

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000323

Gnomad4 OTH

AF:

0.0189

Alfa

AF:

0.0139

Hom.:

Bravo

AF:

0.0309

Asia WGS

AF:

0.00549

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000533

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Glycogen storage disease type X

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 26, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 15, 2016

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

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.82

DANN

Benign

0.87

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over