14-77288878-T-G

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

2

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]

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/exons MANE Protein UniProt
POMT2NM_013382.7 linkuse as main transcriptc.1184-47A>C intron_variant ENST00000261534.9 NP_037514.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
POMT2ENST00000261534.9 linkuse as main transcriptc.1184-47A>C intron_variant 1 NM_013382.7 ENSP00000261534 P1Q9UKY4-1

Frequencies

GnomAD3 genomes
AF:
0.515
AC:
77948
AN:
151408
Hom.:
20390
Cov.:
29
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.:
20
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.:
29
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
Benign, criteria provided, single submitterclinical testingGeneDxJun 14, 2018This 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. -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
not specified Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B2 Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabOct 25, 2021- -
Autosomal recessive limb-girdle muscular dystrophy type 2N Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabOct 25, 2021- -
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A2 Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabOct 25, 2021- -

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.

Other links and lift over

dbSNP: rs2287387; hg19: chr14-77755221; COSMIC: COSV55070251; COSMIC: COSV55070251; API