7-44064620-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DBNL	NM_001014436.3	c.*3704A>G		3_prime_UTR_variant	13/13	ENST00000448521.6
PGAM2	NM_000290.4	c.595+212T>C		intron_variant		ENST00000297283.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DBNL	ENST00000448521.6	c.*3704A>G		3_prime_UTR_variant	13/13	1	NM_001014436.3	P4
PGAM2	ENST00000297283.4	c.595+212T>C		intron_variant		1	NM_000290.4	P1
DBNL	ENST00000432854.5	c.*3704A>G		3_prime_UTR_variant	11/11	5

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

Gnomad4 AFR exome AF: 0.416

Gnomad4 AMR exome AF: 0.294

Gnomad4 ASJ exome AF: 0.238

Gnomad4 EAS exome AF: 0.115

Gnomad4 SAS exome AF: 0.215

Gnomad4 FIN exome AF: 0.308

Gnomad4 NFE exome AF: 0.231

Gnomad4 OTH exome AF: 0.238

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

Gnomad4 AFR AF: 0.425

Gnomad4 AMR AF: 0.286

Gnomad4 ASJ AF: 0.246

Gnomad4 EAS AF: 0.122

Gnomad4 SAS AF: 0.224

Gnomad4 FIN AF: 0.323

Gnomad4 NFE AF: 0.234

Gnomad4 OTH AF: 0.281

Alfa AF: 0.271 Hom.: 970

Bravo AF: 0.298

Asia WGS AF: 0.201 AC: 699 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.23
Dann	Benign	0.19

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

Publications

LitVar

Other links and lift over

dbSNP: rs6956492; hg19: chr7-44104219;