rs3209079

chr14-77278850-A-Cchr14-77278850-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_013382.7(POMT2):c.1911T>G(p.Leu637=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.807 in 1,613,018 control chromosomes in the GnomAD database, including 526,421 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.82 (51439 hom., cov: 33)
  • Exomes 𝑓: 0.81 (474982 hom.)
• Consequence: POMT2 NM_013382.7 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -0.748

Genes affected

POMT2 (HGNC:19743): (protein O-mannosyltransferase 2) The protein encoded by this gene is an O-mannosyltransferase that requires interaction with the product of the POMT1 gene for enzymatic function. The encoded protein is found in the membrane of the endoplasmic reticulum. Defects in this gene are a cause of Walker-Warburg syndrome (WWS).[provided by RefSeq, Oct 2008]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 14-77278850-A-C is Benign according to our data. Variant chr14-77278850-A-C is described in ClinVar as [Benign]. Clinvar id is 166901.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-77278850-A-C is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.748 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.929 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POMT2	NM_013382.7	c.1911T>G	p.Leu637=	synonymous_variant	19/21	ENST00000261534.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POMT2	ENST00000261534.9	c.1911T>G	p.Leu637=	synonymous_variant	19/21	1	NM_013382.7	P1

Frequencies

GnomAD3 genomes AF: 0.821 AC: 124889 AN: 152092 Hom.: 51399 Cov.: 33

Gnomad AFR AF: 0.838

Gnomad AMI AF: 0.849

Gnomad AMR AF: 0.761

Gnomad ASJ AF: 0.831

Gnomad EAS AF: 0.951

Gnomad SAS AF: 0.785

Gnomad FIN AF: 0.857

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.811

Gnomad OTH AF: 0.833

GnomAD3 exomes AF: 0.815 AC: 203865 AN: 250248 Hom.: 83457 AF XY: 0.814 AC XY: 110302 AN XY: 135472

Gnomad AFR exome AF: 0.842

Gnomad AMR exome AF: 0.737

Gnomad ASJ exome AF: 0.819

Gnomad EAS exome AF: 0.964

Gnomad SAS exome AF: 0.775

Gnomad FIN exome AF: 0.847

Gnomad NFE exome AF: 0.814

Gnomad OTH exome AF: 0.814

GnomAD4 exome AF: 0.805 AC: 1176648 AN: 1460808 Hom.: 474982 Cov.: 72 AF XY: 0.805 AC XY: 584837 AN XY: 726742

Gnomad4 AFR exome AF: 0.844

Gnomad4 AMR exome AF: 0.747

Gnomad4 ASJ exome AF: 0.823

Gnomad4 EAS exome AF: 0.967

Gnomad4 SAS exome AF: 0.772

Gnomad4 FIN exome AF: 0.845

Gnomad4 NFE exome AF: 0.801

Gnomad4 OTH exome AF: 0.812

GnomAD4 genome AF: 0.821 AC: 124983 AN: 152210 Hom.: 51439 Cov.: 33 AF XY: 0.823 AC XY: 61244 AN XY: 74428

Gnomad4 AFR AF: 0.838

Gnomad4 AMR AF: 0.760

Gnomad4 ASJ AF: 0.831

Gnomad4 EAS AF: 0.951

Gnomad4 SAS AF: 0.785

Gnomad4 FIN AF: 0.857

Gnomad4 NFE AF: 0.811

Gnomad4 OTH AF: 0.836

Alfa AF: 0.809 Hom.: 31665

Bravo AF: 0.816

Asia WGS AF: 0.874 AC: 3042 AN: 3478

EpiCase AF: 0.809

EpiControl AF: 0.811

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:5

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jun 05, 2013	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Nov 24, 2014	Leu637Leu in exon 19 of POMT2: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. It has been identified in 19.0% (1637/8600) o f European American chromosomes from a broad population by the NHLBI Exome Seque ncing Project (http://evs.gs.washington.edu/EVS; dbSNP rs3209079). -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A2;C3150416:Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B2;C3150418:Autosomal recessive limb-girdle muscular dystrophy type 2N Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Oct 25, 2021

- -

Autosomal recessive limb-girdle muscular dystrophy type 2N Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Oct 25, 2021

- -

Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Oct 25, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	5.7
Dann	Benign	0.55
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs3209079; hg19: chr14-77745193; COSMIC: COSV55071450; COSMIC: COSV55071450;