rs2270421

chr14-77320745-C-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.-64G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 1,562,322 control chromosomes in the GnomAD database, including 66,125 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (5179 hom., cov: 32)
  • Exomes 𝑓: 0.29 (60946 hom.)
• Consequence: POMT2 NM_013382.7 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.694

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=-0.72).
• BP6: Variant 14-77320745-C-T is Benign according to our data. Variant chr14-77320745-C-T is described in ClinVar as [Benign]. Clinvar id is 314564.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POMT2	NM_013382.7	c.-64G>A		5_prime_UTR_variant	1/21	ENST00000261534.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POMT2	ENST00000261534.9	c.-64G>A		5_prime_UTR_variant	1/21	1	NM_013382.7	P1

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37466 AN: 151896 Hom.: 5174 Cov.: 32

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.294

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.413

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.191

Gnomad NFE AF: 0.301

Gnomad OTH AF: 0.222

GnomAD4 exome AF: 0.288 AC: 405477 AN: 1410318 Hom.: 60946 Cov.: 36 AF XY: 0.283 AC XY: 198344 AN XY: 700176

Gnomad4 AFR exome AF: 0.126

Gnomad4 AMR exome AF: 0.186

Gnomad4 ASJ exome AF: 0.228

Gnomad4 EAS exome AF: 0.439

Gnomad4 SAS exome AF: 0.137

Gnomad4 FIN exome AF: 0.366

Gnomad4 NFE exome AF: 0.302

Gnomad4 OTH exome AF: 0.269

GnomAD4 genome AF: 0.247 AC: 37477 AN: 152004 Hom.: 5179 Cov.: 32 AF XY: 0.246 AC XY: 18298 AN XY: 74320

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.199

Gnomad4 ASJ AF: 0.229

Gnomad4 EAS AF: 0.414

Gnomad4 SAS AF: 0.151

Gnomad4 FIN AF: 0.370

Gnomad4 NFE AF: 0.301

Gnomad4 OTH AF: 0.224

Alfa AF: 0.276 Hom.: 4997

Bravo AF: 0.232

Asia WGS AF: 0.251 AC: 869 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

clinical testing

GeneDx

Jun 14, 2018

This 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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
Cadd	Benign	12
Dann	Benign	0.77
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs2270421; hg19: chr14-77787088; COSMIC: COSV53623323; COSMIC: COSV53623323;