14-77285582-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_013382.7(POMT2):c.1383G>A(p.Arg461=) 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 1,613,592 control chromosomes in the GnomAD database, including 526,782 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.83 (52375 hom., cov: 31)
  • Exomes 𝑓: 0.80 (474407 hom.)
• Consequence: POMT2 NM_013382.7 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 0.0250

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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP6: Variant 14-77285582-C-T is Benign according to our data. Variant chr14-77285582-C-T is described in ClinVar as [Benign]. Clinvar id is 166906.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-77285582-C-T is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=0.025 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.1383G>A	p.Arg461=	synonymous_variant	13/21	ENST00000261534.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POMT2	ENST00000261534.9	c.1383G>A	p.Arg461=	synonymous_variant	13/21	1	NM_013382.7	P1

Frequencies

GnomAD3 genomes AF: 0.829 AC: 125885 AN: 151936 Hom.: 52327 Cov.: 31

Gnomad AFR AF: 0.868

Gnomad AMI AF: 0.850

Gnomad AMR AF: 0.762

Gnomad ASJ AF: 0.855

Gnomad EAS AF: 0.951

Gnomad SAS AF: 0.804

Gnomad FIN AF: 0.856

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.806

Gnomad OTH AF: 0.838

GnomAD3 exomes AF: 0.818 AC: 205702 AN: 251466 Hom.: 84589 AF XY: 0.818 AC XY: 111167 AN XY: 135904

Gnomad AFR exome AF: 0.875

Gnomad AMR exome AF: 0.734

Gnomad ASJ exome AF: 0.848

Gnomad EAS exome AF: 0.963

Gnomad SAS exome AF: 0.799

Gnomad FIN exome AF: 0.844

Gnomad NFE exome AF: 0.809

Gnomad OTH exome AF: 0.815

GnomAD4 exome AF: 0.805 AC: 1176143 AN: 1461538 Hom.: 474407 Cov.: 65 AF XY: 0.805 AC XY: 585076 AN XY: 727094

Gnomad4 AFR exome AF: 0.874

Gnomad4 AMR exome AF: 0.744

Gnomad4 ASJ exome AF: 0.852

Gnomad4 EAS exome AF: 0.967

Gnomad4 SAS exome AF: 0.795

Gnomad4 FIN exome AF: 0.842

Gnomad4 NFE exome AF: 0.797

Gnomad4 OTH exome AF: 0.815

GnomAD4 genome AF: 0.829 AC: 125986 AN: 152054 Hom.: 52375 Cov.: 31 AF XY: 0.830 AC XY: 61685 AN XY: 74322

Gnomad4 AFR AF: 0.868

Gnomad4 AMR AF: 0.762

Gnomad4 ASJ AF: 0.855

Gnomad4 EAS AF: 0.951

Gnomad4 SAS AF: 0.804

Gnomad4 FIN AF: 0.856

Gnomad4 NFE AF: 0.806

Gnomad4 OTH AF: 0.841

Alfa AF: 0.812 Hom.: 64049

Bravo AF: 0.825

Asia WGS AF: 0.886 AC: 3082 AN: 3478

EpiCase AF: 0.805

EpiControl AF: 0.806

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	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Nov 24, 2014	Arg461Arg in exon 13 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 19.3% (1664/8600) o f European American chromosomes from a broad population by the NHLBI Exome Seque ncing Project (http://evs.gs.washington.edu/EVS; dbSNP rs2270419). -
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 DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jun 11, 2013	- -
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	-0.38
Cadd	Benign	12
Dann	Benign	0.83
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: rs2270419; hg19: chr14-77751925; COSMIC: COSV55070424; COSMIC: COSV55070424;