14-77277401-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_013382.7(POMT2):​c.2228G>A​(p.Arg743Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,510 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

POMT2
NM_013382.7 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.98
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.17106342).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
POMT2NM_013382.7 linkc.2228G>A p.Arg743Lys missense_variant 21/21 ENST00000261534.9 NP_037514.2 Q9UKY4-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
POMT2ENST00000261534.9 linkc.2228G>A p.Arg743Lys missense_variant 21/211 NM_013382.7 ENSP00000261534.4 Q9UKY4-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.0000119
AC:
3
AN:
251374
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135888
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000980
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000342
AC:
5
AN:
1461510
Hom.:
0
Cov.:
31
AF XY:
0.00000688
AC XY:
5
AN XY:
727106
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000580
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Alfa
AF:
0.000111
Hom.:
0
ExAC
AF:
0.0000165
AC:
2

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsOct 07, 2024The c.2228G>A (p.R743K) alteration is located in exon 21 (coding exon 21) of the POMT2 gene. This alteration results from a G to A substitution at nucleotide position 2228, causing the arginine (R) at amino acid position 743 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.24
T
BayesDel_noAF
Benign
-0.38
CADD
Benign
17
DANN
Benign
0.96
DEOGEN2
Benign
0.33
T
Eigen
Benign
-0.32
Eigen_PC
Benign
-0.076
FATHMM_MKL
Uncertain
0.86
D
LIST_S2
Benign
0.81
T
M_CAP
Benign
0.015
T
MetaRNN
Benign
0.17
T
MetaSVM
Benign
-0.86
T
MutationAssessor
Benign
0.37
N
PrimateAI
Benign
0.44
T
PROVEAN
Benign
0.13
N
REVEL
Benign
0.24
Sift
Benign
0.77
T
Sift4G
Benign
0.94
T
Polyphen
0.0040
B
Vest4
0.053
MutPred
0.45
Gain of catalytic residue at L742 (P = 0);
MVP
0.70
MPC
0.083
ClinPred
0.52
D
GERP RS
5.0
Varity_R
0.20
gMVP
0.55

Splicing

Name
Calibrated prediction
Score
Prediction
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.

Other links and lift over

dbSNP: rs767359121; hg19: chr14-77743744; API