rs7159558

Positions:

• chr14-77276586-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_013382.7(POMT2):​c.*790G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.556 in 152,182 control chromosomes in the GnomAD database, including 23,969 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.56 (23961 hom., cov: 33)
  • Exomes 𝑓: 0.44 (8 hom.)
• Consequence: POMT2 NM_013382.7 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.211

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 14-77276586-C-T is Benign according to our data. Variant chr14-77276586-C-T is described in ClinVar as [Benign]. Clinvar id is 314536.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.595 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POMT2	NM_013382.7	c.*790G>A		3_prime_UTR_variant	21/21	ENST00000261534.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POMT2	ENST00000261534.9	c.*790G>A		3_prime_UTR_variant	21/21	1	NM_013382.7	P1

Frequencies

GnomAD3 genomes AF: 0.556 AC: 84474 AN: 151980 Hom.: 23940 Cov.: 33

Gnomad AFR AF: 0.601

Gnomad AMI AF: 0.557

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.504

Gnomad EAS AF: 0.444

Gnomad SAS AF: 0.453

Gnomad FIN AF: 0.638

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.567

Gnomad OTH AF: 0.533

GnomAD4 exome AF: 0.439 AC: 36 AN: 82 Hom.: 8 Cov.: 0 AF XY: 0.357 AC XY: 20 AN XY: 56

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.688

Gnomad4 NFE exome AF: 0.380

Gnomad4 OTH exome AF: 0.625

GnomAD4 genome AF: 0.556 AC: 84528 AN: 152100 Hom.: 23961 Cov.: 33 AF XY: 0.554 AC XY: 41178 AN XY: 74380

Gnomad4 AFR AF: 0.601

Gnomad4 AMR AF: 0.410

Gnomad4 ASJ AF: 0.504

Gnomad4 EAS AF: 0.445

Gnomad4 SAS AF: 0.453

Gnomad4 FIN AF: 0.638

Gnomad4 NFE AF: 0.567

Gnomad4 OTH AF: 0.538

Alfa AF: 0.550 Hom.: 22164

Bravo AF: 0.540

Asia WGS AF: 0.486 AC: 1688 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Autosomal recessive limb-girdle muscular dystrophy type 2N Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.0
DANN	Benign	0.44

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: rs7159558; hg19: chr14-77742929;