7-44064620-A-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001014436.3(DBNL):​c.*3704A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 591,318 control chromosomes in the GnomAD database, including 20,137 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.29 (7217 hom., cov: 33)
  • Exomes 𝑓: 0.23 (12920 hom.)
• Consequence: DBNL NM_001014436.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.79
• Publications: 4 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BP6: Variant 7-44064620-A-G is Benign according to our data. Variant chr7-44064620-A-G is described in ClinVar as Benign. ClinVar VariationId is 1250168.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

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

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44664 AN: 152074 Hom.: 7188 Cov.: 33

Gnomad AFR AF: 0.425

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.278

GnomAD4 exome AF: 0.235 AC: 103005 AN: 439126 Hom.: 12920 Cov.: 4 AF XY: 0.231 AC XY: 53492 AN XY: 231128

African (AFR) AF: 0.416 AC: 5139 AN: 12366

American (AMR) AF: 0.294 AC: 5880 AN: 20012

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 3235 AN: 13602

East Asian (EAS) AF: 0.115 AC: 3416 AN: 29774

South Asian (SAS) AF: 0.215 AC: 9892 AN: 46108

European-Finnish (FIN) AF: 0.308 AC: 8569 AN: 27830

Middle Eastern (MID) AF: 0.201 AC: 379 AN: 1890

European-Non Finnish (NFE) AF: 0.231 AC: 60478 AN: 262268

Other (OTH) AF: 0.238 AC: 6017 AN: 25276

GnomAD4 genome AF: 0.294 AC: 44757 AN: 152192 Hom.: 7217 Cov.: 33 AF XY: 0.295 AC XY: 21943 AN XY: 74408

African (AFR) AF: 0.425 AC: 17642 AN: 41500

American (AMR) AF: 0.286 AC: 4366 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.246 AC: 854 AN: 3472

East Asian (EAS) AF: 0.122 AC: 636 AN: 5194

South Asian (SAS) AF: 0.224 AC: 1082 AN: 4826

European-Finnish (FIN) AF: 0.323 AC: 3423 AN: 10594

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.234 AC: 15931 AN: 67996

Other (OTH) AF: 0.281 AC: 595 AN: 2116

Alfa AF: 0.271 Hom.: 970

Bravo AF: 0.298

Asia WGS AF: 0.201 AC: 699 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.23
DANN	Benign	0.19
PhyloP100		-2.8
Mutation Taster		=100/0	polymorphism (auto)

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;