14-77275006-C-CT

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_Supporting BS2

The NM_013382.7(POMT2):c.*2369_*2370insA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0215 in 148,336 control chromosomes in the GnomAD database, including 51 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.022 (51 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: POMT2 NM_013382.7 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.370

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]

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0215 (3196/148336) while in subpopulation SAS AF= 0.0492 (231/4692). AF 95% confidence interval is 0.044. There are 51 homozygotes in gnomad4. There are 1637 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High Homozygotes in GnomAd at 51 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POMT2	NM_013382.7	c.*2369_*2370insA		3_prime_UTR_variant	21/21	ENST00000261534.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POMT2	ENST00000261534.9	c.*2369_*2370insA		3_prime_UTR_variant	21/21	1	NM_013382.7	P1

Frequencies

GnomAD3 genomes AF: 0.0216 AC: 3201 AN: 148254 Hom.: 51 Cov.: 32

Gnomad AFR AF: 0.00628

Gnomad AMI AF: 0.00222

Gnomad AMR AF: 0.0364

Gnomad ASJ AF: 0.0601

Gnomad EAS AF: 0.0264

Gnomad SAS AF: 0.0496

Gnomad FIN AF: 0.0212

Gnomad MID AF: 0.0677

Gnomad NFE AF: 0.0230

Gnomad OTH AF: 0.0349

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.0215 AC: 3196 AN: 148336 Hom.: 51 Cov.: 32 AF XY: 0.0226 AC XY: 1637 AN XY: 72310

Gnomad4 AFR AF: 0.00624

Gnomad4 AMR AF: 0.0363

Gnomad4 ASJ AF: 0.0601

Gnomad4 EAS AF: 0.0263

Gnomad4 SAS AF: 0.0492

Gnomad4 FIN AF: 0.0212

Gnomad4 NFE AF: 0.0230

Gnomad4 OTH AF: 0.0341

Bravo AF: 0.0200

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Limb-Girdle Muscular Dystrophy, Recessive Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs113216374; hg19: chr14-77741349;