rs11627257

Positions:

• chr14-77295921-A-C
• chr14-77295921-A-G

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.1116+243T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 151,952 control chromosomes in the GnomAD database, including 5,547 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.24 (5547 hom., cov: 30)
• Consequence: POMT2 NM_013382.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.504

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=-0.89).
• BP6: Variant 14-77295921-A-C is Benign according to our data. Variant chr14-77295921-A-C is described in ClinVar as [Benign]. Clinvar id is 674633.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POMT2	NM_013382.7	c.1116+243T>G		intron_variant		ENST00000261534.9	NP_037514.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POMT2	ENST00000261534.9	c.1116+243T>G		intron_variant		1	NM_013382.7	ENSP00000261534	P1

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36921 AN: 151834 Hom.: 5544 Cov.: 30

Gnomad AFR AF: 0.0843

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.228

Gnomad EAS AF: 0.427

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.405

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.315

Gnomad OTH AF: 0.246

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.243 AC: 36922 AN: 151952 Hom.: 5547 Cov.: 30 AF XY: 0.245 AC XY: 18155 AN XY: 74240

Gnomad4 AFR AF: 0.0843

Gnomad4 AMR AF: 0.209

Gnomad4 ASJ AF: 0.228

Gnomad4 EAS AF: 0.428

Gnomad4 SAS AF: 0.148

Gnomad4 FIN AF: 0.405

Gnomad4 NFE AF: 0.315

Gnomad4 OTH AF: 0.248

Alfa AF: 0.183 Hom.: 449

Bravo AF: 0.225

Asia WGS AF: 0.250 AC: 866 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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	-0.89
CADD	Benign	7.2
DANN	Benign	0.72

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: rs11627257; hg19: chr14-77762264;