rs4540995

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_013382.7(POMT2):c.1654-6A>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 1,614,048 control chromosomes in the GnomAD database, including 10,268 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1827 hom., cov: 32)

Exomes 𝑓: 0.10 ( 8441 hom. )

Consequence

POMT2
NM_013382.7 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0001492

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:14

Conservation

PhyloP100: 0.567

Variant links:

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]

POMT2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant 14-77280469-T-C is Benign according to our data. Variant chr14-77280469-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 95537.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-77280469-T-C is described in Lovd as [Benign]. Variant chr14-77280469-T-C is described in Lovd as [Likely_pathogenic].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.228 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POMT2	NM_013382.7 linkuse as main transcript	c.1654-6A>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000261534.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POMT2	ENST00000261534.9 linkuse as main transcript	c.1654-6A>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_013382.7	P1	Q9UKY4-1

Frequencies

GnomAD3 genomes

AF:

0.140

AC:

21260

AN:

152088

Hom.:

1821

Cov.:

show subpopulations

Gnomad AFR

AF:

0.232

Gnomad AMI

AF:

0.0724

Gnomad AMR

AF:

0.0931

Gnomad ASJ

AF:

0.0910

Gnomad EAS

AF:

0.214

Gnomad SAS

AF:

0.0556

Gnomad FIN

AF:

0.108

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.104

Gnomad OTH

AF:

0.124

GnomAD3 exomes

AF:

0.109

AC:

27303

AN:

251418

Hom.:

1919

AF XY:

0.104

AC XY:

14187

AN XY:

135884

show subpopulations

Gnomad AFR exome

AF:

0.241

Gnomad AMR exome

AF:

0.0614

Gnomad ASJ exome

AF:

0.0934

Gnomad EAS exome

AF:

0.225

Gnomad SAS exome

AF:

0.0513

Gnomad FIN exome

AF:

0.108

Gnomad NFE exome

AF:

0.103

Gnomad OTH exome

AF:

0.101

GnomAD4 exome

AF:

0.100

AC:

146541

AN:

1461842

Hom.:

8441

Cov.:

AF XY:

0.0984

AC XY:

71594

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.243

Gnomad4 AMR exome

AF:

0.0638

Gnomad4 ASJ exome

AF:

0.0974

Gnomad4 EAS exome

AF:

0.230

Gnomad4 SAS exome

AF:

0.0520

Gnomad4 FIN exome

AF:

0.104

Gnomad4 NFE exome

AF:

0.0962

Gnomad4 OTH exome

AF:

0.105

GnomAD4 genome

AF:

0.140

AC:

21288

AN:

152206

Hom.:

1827

Cov.:

AF XY:

0.138

AC XY:

10296

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.232

Gnomad4 AMR

AF:

0.0928

Gnomad4 ASJ

AF:

0.0910

Gnomad4 EAS

AF:

0.214

Gnomad4 SAS

AF:

0.0559

Gnomad4 FIN

AF:

0.108

Gnomad4 NFE

AF:

0.104

Gnomad4 OTH

AF:

0.123

Alfa

AF:

0.106

Hom.:

1626

Bravo

AF:

0.144

Asia WGS

AF:

0.110

AC:

385

AN:

3478

EpiCase

AF:

0.102

EpiControl

AF:

0.107

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:14

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:7

Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
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	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Nov 26, 2014	c.1654-6A>G in intron 15 of POMT2: This variant is not expected to have clinical significance because it has been identified in 23% (1034/4406) of African Ameri can chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington. edu/EVS/; dbSNP rs4540995). -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 18, 2012	- -

Autosomal recessive limb-girdle muscular dystrophy type 2N

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Oct 25, 2021	- -
Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Apr 27, 2017	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	May 01, 2017	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

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

- -

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

-0.46

Cadd

Benign

7.0

Dann

Benign

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00015

dbscSNV1_RF

Benign

0.028

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over