7-44065189-A-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000290.4(PGAM2):c.341T>G(p.Ile114Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0159 in 1,613,994 control chromosomes in the GnomAD database, including 827 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.027 ( 132 hom., cov: 33)

Exomes 𝑓: 0.015 ( 695 hom. )

Consequence

PGAM2
NM_000290.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 7.25

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0065627396).

BP6

Variant 7-44065189-A-C is Benign according to our data. Variant chr7-44065189-A-C is described in ClinVar as [Benign]. Clinvar id is 360276.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-44065189-A-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0968 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGAM2	NM_000290.4 link	c.341T>G	p.Ile114Ser	missense_variant	Exon 1 of 3	ENST00000297283.4	NP_000281.2	P15259
DBNL	NM_001014436.3 link	c.*4273A>C		3_prime_UTR_variant	Exon 13 of 13	ENST00000448521.6	NP_001014436.1	Q9UJU6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PGAM2	ENST00000297283.4 link	c.341T>G	p.Ile114Ser	missense_variant	Exon 1 of 3	1	NM_000290.4	ENSP00000297283.3		P15259
DBNL	ENST00000448521.6 link	c.*4273A>C		3_prime_UTR_variant	Exon 13 of 13	1	NM_001014436.3	ENSP00000411701.1		Q9UJU6-1

Frequencies

GnomAD3 genomes

AF:

0.0271

AC:

4129

AN:

152088

Hom.:

130

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0595

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0172

Gnomad ASJ

AF:

0.0357

Gnomad EAS

AF:

0.0488

Gnomad SAS

AF:

0.103

Gnomad FIN

AF:

0.000660

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.00622

Gnomad OTH

AF:

0.0335

GnomAD3 exomes

AF:

0.0273

AC:

6860

AN:

251284

Hom.:

250

AF XY:

0.0301

AC XY:

4089

AN XY:

135866

show subpopulations

Gnomad AFR exome

AF:

0.0612

Gnomad AMR exome

AF:

0.0181

Gnomad ASJ exome

AF:

0.0345

Gnomad EAS exome

AF:

0.0506

Gnomad SAS exome

AF:

0.0977

Gnomad FIN exome

AF:

0.000694

Gnomad NFE exome

AF:

0.00700

Gnomad OTH exome

AF:

0.0267

GnomAD4 exome

AF:

0.0148

AC:

21562

AN:

1461788

Hom.:

695

Cov.:

AF XY:

0.0170

AC XY:

12397

AN XY:

727206

show subpopulations

Gnomad4 AFR exome

AF:

0.0667

Gnomad4 AMR exome

AF:

0.0185

Gnomad4 ASJ exome

AF:

0.0346

Gnomad4 EAS exome

AF:

0.0428

Gnomad4 SAS exome

AF:

0.0957

Gnomad4 FIN exome

AF:

0.000750

Gnomad4 NFE exome

AF:

0.00511

Gnomad4 OTH exome

AF:

0.0239

GnomAD4 genome

AF:

0.0272

AC:

4146

AN:

152206

Hom.:

132

Cov.:

AF XY:

0.0282

AC XY:

2100

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.0596

Gnomad4 AMR

AF:

0.0172

Gnomad4 ASJ

AF:

0.0357

Gnomad4 EAS

AF:

0.0487

Gnomad4 SAS

AF:

0.104

Gnomad4 FIN

AF:

0.000660

Gnomad4 NFE

AF:

0.00622

Gnomad4 OTH

AF:

0.0336

Alfa

AF:

0.0139

Hom.:

Bravo

AF:

0.0288

TwinsUK

AF:

0.00378

AC:

ALSPAC

AF:

0.00597

AC:

ESP6500AA

AF:

0.0502

AC:

221

ESP6500EA

AF:

0.00628

AC:

ExAC

AF:

0.0289

AC:

3505

Asia WGS

AF:

0.0690

AC:

239

AN:

3478

EpiCase

AF:

0.0112

EpiControl

AF:

0.0111

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 01, 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. -

not provided

Benign:2

Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Mar 13, 2017	- -

Glycogen storage disease type X

Benign:2

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. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 03, 2025	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.79

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.17

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.66

Eigen

Pathogenic

0.84

Eigen_PC

Pathogenic

0.82

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.97

MetaRNN

Benign

0.0066

MetaSVM

Benign

-0.50

MutationAssessor

Uncertain

2.4

PrimateAI

Uncertain

0.65

PROVEAN

Pathogenic

-5.4

REVEL

Uncertain

0.59

Sift

Uncertain

0.0080

Sift4G

Uncertain

0.0030

Polyphen

0.99

Vest4

0.34

MPC

0.51

ClinPred

0.013

GERP RS

5.9

Varity_R

0.87

gMVP

0.80

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.

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