Genetic Variant POMT2:c.1184-47A>C (chr14-77288878-T-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_013382.7(POMT2):c.1184-47A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.53 in 1,526,204 control chromosomes in the GnomAD database, including 217,298 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.51 ( 20408 hom., cov: 29)

Exomes 𝑓: 0.53 ( 196890 hom. )

Consequence

POMT2
NM_013382.7 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.827

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=-0.89).

BP6

Variant 14-77288878-T-G is Benign according to our data. Variant chr14-77288878-T-G is described in ClinVar as [Benign]. Clinvar id is 260290.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-77288878-T-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POMT2	NM_013382.7 link	c.1184-47A>C		intron_variant	Intron 10 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.1184-47A>C		intron_variant	Intron 10 of 20	1	NM_013382.7	ENSP00000261534.4		Q9UKY4-1

Frequencies

GnomAD3 genomes

AF:

0.515

AC:

77948

AN:

151408

Hom.:

20390

Cov.:

show subpopulations

Gnomad AFR

AF:

0.480

Gnomad AMI

AF:

0.570

Gnomad AMR

AF:

0.397

Gnomad ASJ

AF:

0.485

Gnomad EAS

AF:

0.456

Gnomad SAS

AF:

0.474

Gnomad FIN

AF:

0.616

Gnomad MID

AF:

0.481

Gnomad NFE

AF:

0.555

Gnomad OTH

AF:

0.500

GnomAD3 exomes

AF:

0.499

AC:

124783

AN:

249944

Hom.:

32269

AF XY:

0.506

AC XY:

68404

AN XY:

135152

show subpopulations

Gnomad AFR exome

AF:

0.484

Gnomad AMR exome

AF:

0.313

Gnomad ASJ exome

AF:

0.475

Gnomad EAS exome

AF:

0.458

Gnomad SAS exome

AF:

0.466

Gnomad FIN exome

AF:

0.615

Gnomad NFE exome

AF:

0.554

Gnomad OTH exome

AF:

0.507

GnomAD4 exome

AF:

0.531

AC:

730333

AN:

1374678

Hom.:

196890

Cov.:

AF XY:

0.531

AC XY:

365598

AN XY:

689012

show subpopulations

Gnomad4 AFR exome

AF:

0.479

Gnomad4 AMR exome

AF:

0.321

Gnomad4 ASJ exome

AF:

0.485

Gnomad4 EAS exome

AF:

0.470

Gnomad4 SAS exome

AF:

0.465

Gnomad4 FIN exome

AF:

0.608

Gnomad4 NFE exome

AF:

0.548

Gnomad4 OTH exome

AF:

0.516

GnomAD4 genome

AF:

0.515

AC:

78004

AN:

151526

Hom.:

20408

Cov.:

AF XY:

0.514

AC XY:

38021

AN XY:

74024

show subpopulations

Gnomad4 AFR

AF:

0.480

Gnomad4 AMR

AF:

0.396

Gnomad4 ASJ

AF:

0.485

Gnomad4 EAS

AF:

0.457

Gnomad4 SAS

AF:

0.475

Gnomad4 FIN

AF:

0.616

Gnomad4 NFE

AF:

0.555

Gnomad4 OTH

AF:

0.504

Alfa

AF:

0.538

Hom.:

5528

Bravo

AF:

0.494

Asia WGS

AF:

0.486

AC:

1691

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 14, 2018

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. -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

Benign:1

Oct 25, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autosomal recessive limb-girdle muscular dystrophy type 2N

Benign:1

Oct 25, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

Benign:1

Oct 25, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.20

DANN

Benign

0.55

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

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