rs369654108

Variant names:

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM1BP4_ModerateBP6BS1BS2

The NM_013382.7(POMT2):c.629T>C(p.Met210Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000119 in 1,613,538 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00013 ( 4 hom. )

Consequence

POMT2
NM_013382.7 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:3B:2

Conservation

PhyloP100: 8.98

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 -9 ACMG points.

PM1

In a transmembrane_region Helical (size 20) in uniprot entity POMT2_HUMAN there are 4 pathogenic changes around while only 0 benign (100%) in NM_013382.7

BP4

Computational evidence support a benign effect (MetaRNN=0.07689169).

BP6

Variant 14-77302862-A-G is Benign according to our data. Variant chr14-77302862-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 224703.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Benign=1, Uncertain_significance=3}.

BS1

Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.000127 (186/1461238) while in subpopulation SAS AF= 0.00201 (173/86224). AF 95% confidence interval is 0.00176. There are 4 homozygotes in gnomad4_exome. There are 139 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POMT2	NM_013382.7 link	c.629T>C	p.Met210Thr	missense_variant	Exon 5 of 21	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.629T>C	p.Met210Thr	missense_variant	Exon 5 of 21	1	NM_013382.7	ENSP00000261534.4		Q9UKY4-1

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000263

AC:

AN:

251154

Hom.:

AF XY:

0.000383

AC XY:

AN XY:

135770

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00212

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000127

AC:

186

AN:

1461238

Hom.:

Cov.:

AF XY:

0.000191

AC XY:

139

AN XY:

726972

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00201

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152300

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.000264

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:3Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:2Benign:1

Apr 28, 2021

Athena Diagnostics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 07, 2017

Genetic Services Laboratory, University of Chicago

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dec 01, 2015

Center for Genetic Medicine Research, Children's National Medical Center

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: research

- -

not provided

Uncertain:1

Dec 03, 2019

GeneDx

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Reported previously in the heterozygous state as a variant of uncertain significance, along with a NEB variant of uncertain significance, in a patient with congenital muscular dystrophy (Punetha et al., 2016); This variant is associated with the following publications: (PMID: 27854218) -

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

Mar 02, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Uncertain

0.050

CADD

Uncertain

DANN

Benign

0.93

DEOGEN2

Uncertain

0.70

D;D

Eigen

Benign

0.11

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.82

T;T

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.077

T;T

MetaSVM

Uncertain

-0.24

MutationAssessor

Benign

1.2

L;.

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-2.3

N;D

REVEL

Uncertain

0.62

Sift

Benign

0.10

T;T

Sift4G

Benign

0.18

T;T

Polyphen

0.13

B;.

Vest4

0.94

MutPred

0.62

Gain of catalytic residue at A205 (P = 0);.;

MVP

0.84

MPC

0.14

ClinPred

0.18

GERP RS

4.4

Varity_R

0.37

gMVP

0.78

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