14-77302842-C-T

Position:

chr14-77302842-C-T

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_StrongBP6BS1

The ENST00000261534.9(POMT2):c.649G>A(p.Ala217Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000117 in 1,611,170 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. A217A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00063 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000063 ( 0 hom. )

Consequence

POMT2
ENST00000261534.9 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.02

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 -7 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.004279852).

BP6

Variant 14-77302842-C-T is Benign according to our data. Variant chr14-77302842-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 282839.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=3, Likely_benign=2}.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000631 (96/152242) while in subpopulation AFR AF= 0.00205 (85/41538). AF 95% confidence interval is 0.00169. There are 0 homozygotes in gnomad4. There are 44 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POMT2	NM_013382.7 linkuse as main transcript	c.649G>A	p.Ala217Thr	missense_variant	5/21	ENST00000261534.9	NP_037514.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POMT2	ENST00000261534.9 linkuse as main transcript	c.649G>A	p.Ala217Thr	missense_variant	5/21	1	NM_013382.7	ENSP00000261534	P1	Q9UKY4-1

Frequencies

GnomAD3 genomes

AF:

0.000624

AC:

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00203

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.000203

AC:

AN:

250816

Hom.:

AF XY:

0.000155

AC XY:

AN XY:

135594

show subpopulations

Gnomad AFR exome

AF:

0.00302

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000631

AC:

AN:

1458928

Hom.:

Cov.:

AF XY:

0.0000606

AC XY:

AN XY:

725954

show subpopulations

Gnomad4 AFR exome

AF:

0.00251

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000451

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.000631

AC:

AN:

152242

Hom.:

Cov.:

AF XY:

0.000591

AC XY:

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.00205

Gnomad4 AMR

AF:

0.000458

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.000140

Hom.:

Bravo

AF:

0.000684

ESP6500AA

AF:

0.00318

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000321

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:3Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:3Benign:1

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 26, 2021	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Apr 20, 2017	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Oct 06, 2020	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Revvity Omics, Revvity	Jul 13, 2022	- -

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

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 26, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.18

T;T

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.62

LIST_S2

Benign

0.75

T;T

M_CAP

Benign

0.047

MetaRNN

Benign

0.0043

T;T

MetaSVM

Benign

-0.57

MutationAssessor

Benign

0.47

N;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.41

PROVEAN

Benign

0.040

N;N

REVEL

Benign

0.18

Sift

Benign

0.58

T;T

Sift4G

Benign

0.54

T;T

Polyphen

0.0010

B;.

Vest4

0.18

MVP

0.72

MPC

0.080

ClinPred

0.014

GERP RS

3.7

Varity_R

0.054

gMVP

0.23

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