7-44065206-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

0 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
PGAM2	NM_000290.4 link	c.324G>A	p.Gly108Gly	synonymous_variant	Exon 1 of 3	ENST00000297283.4	NP_000281.2	P15259
DBNL	NM_001014436.3 link	c.*4290C>T		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.324G>A	p.Gly108Gly	synonymous_variant	Exon 1 of 3	1	NM_000290.4	ENSP00000297283.3		P15259
DBNL	ENST00000448521.6 link	c.*4290C>T		3_prime_UTR_variant	Exon 13 of 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

GnomAD2 exomes

AF:

0.00711

AC:

1786

AN:

251298

AF XY:

0.00508

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 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

African (AFR)

AF:

0.0941

AC:

3151

AN:

33480

American (AMR)

AF:

0.00474

AC:

212

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000139

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.0000188

AC:

AN:

53302

Middle Eastern (MID)

AF:

0.00243

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000136

AC:

151

AN:

1112006

Other (OTH)

AF:

0.00580

AC:

350

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

276

553

829

1106

1382

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

208

312

416

520

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0271

AC:

4128

AN:

152280

Hom.:

195

Cov.:

AF XY:

0.0257

AC XY:

1916

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.0951

AC:

3950

AN:

41546

American (AMR)

AF:

0.00745

AC:

114

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.000207

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000323

AC:

AN:

68020

Other (OTH)

AF:

0.0189

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

193

386

578

771

964

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

168

210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0134

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

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Mar 15, 2016

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

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.82

(source)

DANN

Benign

0.87

PhyloP100

-3.6

PromoterAI

0.0023

Neutral

(source)

Mutation Taster

=97/3

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over