Genetic Variant POMT2:c.2148-18A>G (chr14-77277499-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_013382.7(POMT2):c.2148-18A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00522 in 1,580,396 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0035 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0054 ( 27 hom. )

Consequence

POMT2
NM_013382.7 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.07

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 14-77277499-T-C is Benign according to our data. Variant chr14-77277499-T-C is described in ClinVar as [Benign]. Clinvar id is 138787.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-77277499-T-C is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0035 (533/152260) while in subpopulation SAS AF= 0.00705 (34/4820). AF 95% confidence interval is 0.00559. There are 2 homozygotes in gnomad4. There are 257 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POMT2	NM_013382.7 link	c.2148-18A>G		intron_variant	Intron 20 of 20	ENST00000261534.9	NP_037514.2	Q9UKY4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POMT2	ENST00000261534.9 link	c.2148-18A>G		intron_variant	Intron 20 of 20	1	NM_013382.7	ENSP00000261534.4		Q9UKY4-1

Frequencies

GnomAD3 genomes

AF:

0.00350

AC:

533

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00106

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00705

Gnomad FIN

AF:

0.00113

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00607

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.00413

AC:

1036

AN:

250806

Hom.:

AF XY:

0.00439

AC XY:

595

AN XY:

135662

show subpopulations

Gnomad AFR exome

AF:

0.000862

Gnomad AMR exome

AF:

0.00116

Gnomad ASJ exome

AF:

0.00119

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00797

Gnomad FIN exome

AF:

0.000786

Gnomad NFE exome

AF:

0.00608

Gnomad OTH exome

AF:

0.00342

GnomAD4 exome

AF:

0.00540

AC:

7710

AN:

1428136

Hom.:

Cov.:

AF XY:

0.00540

AC XY:

3847

AN XY:

712424

show subpopulations

Gnomad4 AFR exome

AF:

0.000827

Gnomad4 AMR exome

AF:

0.00121

Gnomad4 ASJ exome

AF:

0.00189

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00817

Gnomad4 FIN exome

AF:

0.00107

Gnomad4 NFE exome

AF:

0.00611

Gnomad4 OTH exome

AF:

0.00359

GnomAD4 genome

AF:

0.00350

AC:

533

AN:

152260

Hom.:

Cov.:

AF XY:

0.00345

AC XY:

257

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.00106

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.00288

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00705

Gnomad4 FIN

AF:

0.00113

Gnomad4 NFE

AF:

0.00607

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.00316

Hom.:

Bravo

AF:

0.00342

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Mar 14, 2014

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.22

DANN

Benign

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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