7-44062806-CCG-ACC

Variant names:

• chr7-44062806-CCG-ACC
• NM_000290.4:c.718_720delCGGinsGGT
• PGAM2 p.Arg240Gly

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_000290.4(PGAM2):​c.718_720delCGGinsGGT​(p.Arg240Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R240Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PGAM2 NM_000290.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.78
• 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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.718_720delCGGinsGGT	p.Arg240Gly	missense	N/A	NP_000281.2	P15259
	DBNL	NM_001014436.3	MANE Select	c.*1890_*1892delCCGinsACC		3_prime_UTR	Exon 13 of 13	NP_001014436.1	Q9UJU6-1
	DBNL	NM_001122956.2		c.*1890_*1892delCCGinsACC		3_prime_UTR	Exon 13 of 13	NP_001116428.1	Q9UJU6-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGAM2	ENST00000297283.4	TSL:1 MANE Select	c.718_720delCGGinsGGT	p.Arg240Gly	missense	N/A	ENSP00000297283.3	P15259
	DBNL	ENST00000448521.6	TSL:1 MANE Select	c.*1890_*1892delCCGinsACC		3_prime_UTR	Exon 13 of 13	ENSP00000411701.1	Q9UJU6-1
	PGAM2	ENST00000971360.1		c.715_717delCGGinsGGT	p.Arg239Gly	missense	N/A	ENSP00000641419.1

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.8

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr7-44102405;