rs2363640

Positions:

• chr14-77312990-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013382.7(POMT2):​c.249-957A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.826 in 152,264 control chromosomes in the GnomAD database, including 52,095 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.83 (52095 hom., cov: 34)
• Consequence: POMT2 NM_013382.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.919

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.93 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POMT2	NM_013382.7	c.249-957A>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.249-957A>G		intron_variant		1	NM_013382.7	ENSP00000261534	P1

Frequencies

GnomAD3 genomes AF: 0.826 AC: 125609 AN: 152146 Hom.: 52049 Cov.: 34

Gnomad AFR AF: 0.874

Gnomad AMI AF: 0.871

Gnomad AMR AF: 0.741

Gnomad ASJ AF: 0.822

Gnomad EAS AF: 0.951

Gnomad SAS AF: 0.817

Gnomad FIN AF: 0.882

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.797

Gnomad OTH AF: 0.822

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

GnomAD4 genome AF: 0.826 AC: 125710 AN: 152264 Hom.: 52095 Cov.: 34 AF XY: 0.828 AC XY: 61636 AN XY: 74442

Gnomad4 AFR AF: 0.874

Gnomad4 AMR AF: 0.741

Gnomad4 ASJ AF: 0.822

Gnomad4 EAS AF: 0.952

Gnomad4 SAS AF: 0.816

Gnomad4 FIN AF: 0.882

Gnomad4 NFE AF: 0.797

Gnomad4 OTH AF: 0.824

Alfa AF: 0.798 Hom.: 46913

Bravo AF: 0.818

Asia WGS AF: 0.888 AC: 3091 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.20
DANN	Benign	0.83

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: rs2363640; hg19: chr14-77779333;