chr14-77275628-G-T

Position:

• chr14-77275628-G-T

Variant summary

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

The NM_013382.7(POMT2):​c.*1748C>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 0.107 in 152,246 control chromosomes in the GnomAD database, including 1,804 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1804 hom., cov: 32)
  • Exomes 𝑓: 0.025 (0 hom.)
• Consequence: POMT2 NM_013382.7 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.631

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=-0.85).
• BP6: Variant 14-77275628-G-T is Benign according to our data. Variant chr14-77275628-G-T is described in ClinVar as [Benign]. Clinvar id is 314519.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POMT2	NM_013382.7	c.*1748C>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.*1748C>A		3_prime_UTR_variant	21/21	1	NM_013382.7	ENSP00000261534	P1

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16347 AN: 151968 Hom.: 1803 Cov.: 32

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.0533

Gnomad ASJ AF: 0.0479

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0473

Gnomad FIN AF: 0.0516

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0359

Gnomad OTH AF: 0.102

GnomAD4 exome AF: 0.0250 AC: 4 AN: 160 Hom.: 0 Cov.: 0 AF XY: 0.0364 AC XY: 4 AN XY: 110

Gnomad4 ASJ exome AF: 0.00

Gnomad4 FIN exome AF: 0.0357

Gnomad4 NFE exome AF: 0.0306

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.108 AC: 16359 AN: 152086 Hom.: 1804 Cov.: 32 AF XY: 0.105 AC XY: 7803 AN XY: 74366

Gnomad4 AFR AF: 0.287

Gnomad4 AMR AF: 0.0532

Gnomad4 ASJ AF: 0.0479

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.0469

Gnomad4 FIN AF: 0.0516

Gnomad4 NFE AF: 0.0359

Gnomad4 OTH AF: 0.100

Alfa AF: 0.0768 Hom.: 144

Bravo AF: 0.117

Asia WGS AF: 0.0380 AC: 131 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 12, 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	-0.85
CADD	Benign	0.82
DANN	Benign	0.58

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: rs45458096; hg19: chr14-77741971;