7-44065206-C-T

Variant names:

• chr7-44065206-C-T
• rs112828964
• NM_000290.4:c.324G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -3.64
• Publications: 0 publications found

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]

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]

ENSG00000239775 (HGNC:):

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000290.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGAM2	NM_000290.4	MANE Select	c.324G>A	p.Gly108Gly	synonymous	Exon 1 of 3	NP_000281.2
	DBNL	NM_001014436.3	MANE Select	c.*4290C>T		3_prime_UTR	Exon 13 of 13	NP_001014436.1
	DBNL	NM_001122956.2		c.*4290C>T		3_prime_UTR	Exon 13 of 13	NP_001116428.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGAM2	ENST00000297283.4	TSL:1 MANE Select	c.324G>A	p.Gly108Gly	synonymous	Exon 1 of 3	ENSP00000297283.3
	DBNL	ENST00000448521.6	TSL:1 MANE Select	c.*4290C>T		3_prime_UTR	Exon 13 of 13	ENSP00000411701.1
	PGAM2	ENST00000971360.1		c.324G>A	p.Gly108Gly	synonymous	Exon 1 of 3	ENSP00000641419.1

Frequencies

GnomAD3 genomes AF: 0.0271 AC: 4118 AN: 152162 Hom.: 194 Cov.: 33

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

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.: 35 AF XY: 0.00220 AC XY: 1603 AN XY: 727204

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: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000139 AC: 12 AN: 86258

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53302

Middle Eastern (MID) AF: 0.00243 AC: 14 AN: 5768

European-Non Finnish (NFE) AF: 0.000136 AC: 151 AN: 1112006

Other (OTH) AF: 0.00580 AC: 350 AN: 60396

GnomAD4 genome AF: 0.0271 AC: 4128 AN: 152280 Hom.: 195 Cov.: 33 AF XY: 0.0257 AC XY: 1916 AN XY: 74474

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: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000323 AC: 22 AN: 68020

Other (OTH) AF: 0.0189 AC: 40 AN: 2112

Alfa AF: 0.0134 Hom.: 63

Bravo AF: 0.0309

Asia WGS AF: 0.00549 AC: 19 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000533

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Glycogen storage disease type X (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.82
DANN	Benign	0.87
PhyloP100		-3.6
PromoterAI		0.0023	Neutral
Mutation Taster		=97/3	polymorphism (auto)

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

Other links and lift over

dbSNP: rs112828964; hg19: chr7-44104805;