rs6956492

Variant names:

• chr7-44064620-A-C
• rs6956492
• NM_001014436.3:c.*3704A>C

Your query was ambiguous. Multiple possible variants found:

• chr7-44064620-A-C
• chr7-44064620-A-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001014436.3(DBNL):​c.*3704A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000455 in 439,566 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000045 (0 hom.)
• Consequence: DBNL NM_001014436.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.79
• Publications: 0 publications found

Genes affected

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]

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 Gene-Disease associations (from GenCC):

• glycogen storage disease due to phosphoglycerate mutase deficiency

  Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp, PanelApp Australia, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001014436.3. 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
	DBNL	NM_001014436.3	MANE Select	c.*3704A>C		3_prime_UTR	Exon 13 of 13	NP_001014436.1	Q9UJU6-1
	PGAM2	NM_000290.4	MANE Select	c.595+212T>G		intron	N/A	NP_000281.2	P15259
	DBNL	NM_001122956.2		c.*3704A>C		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
	DBNL	ENST00000448521.6	TSL:1 MANE Select	c.*3704A>C		3_prime_UTR	Exon 13 of 13	ENSP00000411701.1	Q9UJU6-1
	PGAM2	ENST00000297283.4	TSL:1 MANE Select	c.595+212T>G		intron	N/A	ENSP00000297283.3	P15259
	DBNL	ENST00000432854.5	TSL:5	c.*3704A>C		3_prime_UTR	Exon 11 of 11	ENSP00000398931.1	H0Y5J4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000455 AC: 2 AN: 439566 Hom.: 0 Cov.: 4 AF XY: 0.00000432 AC XY: 1 AN XY: 231334

African (AFR) AF: 0.00 AC: 0 AN: 12378

American (AMR) AF: 0.00 AC: 0 AN: 20046

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13616

East Asian (EAS) AF: 0.00 AC: 0 AN: 29792

South Asian (SAS) AF: 0.00 AC: 0 AN: 46114

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27878

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1894

European-Non Finnish (NFE) AF: 0.00000762 AC: 2 AN: 262558

Other (OTH) AF: 0.00 AC: 0 AN: 25290

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.21
DANN	Benign	0.24
PhyloP100		-2.8

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

Other links and lift over

dbSNP: rs6956492; hg19: chr7-44104219;