14-77275634-C-T

Position:

• chr14-77275634-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000261534.9(POMT2):​c.*1742G>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 0.825 in 152,216 control chromosomes in the GnomAD database, including 52,082 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.83 (52042 hom., cov: 30)
  • Exomes 𝑓: 0.78 (40 hom.)
• Consequence: POMT2 ENST00000261534.9 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.21

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 14-77275634-C-T is Benign according to our data. Variant chr14-77275634-C-T is described in ClinVar as [Benign]. Clinvar id is 314520.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.929 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POMT2	NM_013382.7	c.*1742G>A		3_prime_UTR_variant	21/21	ENST00000261534.9	NP_037514.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POMT2	ENST00000261534.9	c.*1742G>A		3_prime_UTR_variant	21/21	1	NM_013382.7	ENSP00000261534	P1

Frequencies

GnomAD3 genomes AF: 0.826 AC: 125450 AN: 151968 Hom.: 51994 Cov.: 30

Gnomad AFR AF: 0.876

Gnomad AMI AF: 0.849

Gnomad AMR AF: 0.762

Gnomad ASJ AF: 0.851

Gnomad EAS AF: 0.951

Gnomad SAS AF: 0.782

Gnomad FIN AF: 0.840

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.799

Gnomad OTH AF: 0.837

GnomAD4 exome AF: 0.785 AC: 102 AN: 130 Hom.: 40 Cov.: 0 AF XY: 0.744 AC XY: 58 AN XY: 78

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.792

Gnomad4 NFE exome AF: 0.814

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.826 AC: 125552 AN: 152086 Hom.: 52042 Cov.: 30 AF XY: 0.826 AC XY: 61430 AN XY: 74342

Gnomad4 AFR AF: 0.876

Gnomad4 AMR AF: 0.761

Gnomad4 ASJ AF: 0.851

Gnomad4 EAS AF: 0.951

Gnomad4 SAS AF: 0.781

Gnomad4 FIN AF: 0.840

Gnomad4 NFE AF: 0.799

Gnomad4 OTH AF: 0.839

Alfa AF: 0.792 Hom.: 6212

Bravo AF: 0.824

Asia WGS AF: 0.877 AC: 3052 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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. -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.64
DANN	Benign	0.42

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

Other links and lift over

dbSNP: rs12894594; hg19: chr14-77741977;