rs972725

Variant names:

• chr14-77281968-A-G
• rs972725
• NM_013382.7:c.1654-1505T>C

Your query was ambiguous. Multiple possible variants found:

• chr14-77281968-A-G
• chr14-77281968-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013382.7(POMT2):​c.1654-1505T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.828 in 152,114 control chromosomes in the GnomAD database, including 52,383 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 (52383 hom., cov: 32)
• Consequence: POMT2 NM_013382.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16
• Publications: 1 publications found

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]

POMT2 Gene-Disease associations (from GenCC):

• muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A2

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• myopathy caused by variation in POMT2

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B2

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics
• autosomal recessive limb-girdle muscular dystrophy type 2N

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• congenital muscular dystrophy with cerebellar involvement

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• congenital muscular dystrophy with intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• muscle-eye-brain disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• muscular dystrophy-dystroglycanopathy, type A

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• 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 rank	MANE	Protein	UniProt
POMT2	NM_013382.7	c.1654-1505T>C		intron_variant	Intron 15 of 20	ENST00000261534.9	NP_037514.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POMT2	ENST00000261534.9	c.1654-1505T>C		intron_variant	Intron 15 of 20	1	NM_013382.7	ENSP00000261534.4

Frequencies

GnomAD3 genomes AF: 0.828 AC: 125926 AN: 151996 Hom.: 52339 Cov.: 32

Gnomad AFR AF: 0.867

Gnomad AMI AF: 0.849

Gnomad AMR AF: 0.763

Gnomad ASJ AF: 0.855

Gnomad EAS AF: 0.951

Gnomad SAS AF: 0.805

Gnomad FIN AF: 0.855

Gnomad MID AF: 0.761

Gnomad NFE AF: 0.806

Gnomad OTH AF: 0.841

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

GnomAD4 genome AF: 0.828 AC: 126022 AN: 152114 Hom.: 52383 Cov.: 32 AF XY: 0.830 AC XY: 61686 AN XY: 74342

African (AFR) AF: 0.867 AC: 35973 AN: 41482

American (AMR) AF: 0.762 AC: 11639 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.855 AC: 2969 AN: 3472

East Asian (EAS) AF: 0.952 AC: 4927 AN: 5178

South Asian (SAS) AF: 0.805 AC: 3874 AN: 4814

European-Finnish (FIN) AF: 0.855 AC: 9052 AN: 10582

Middle Eastern (MID) AF: 0.760 AC: 222 AN: 292

European-Non Finnish (NFE) AF: 0.806 AC: 54814 AN: 67996

Other (OTH) AF: 0.843 AC: 1778 AN: 2110

Alfa AF: 0.834 Hom.: 6851

Bravo AF: 0.825

Asia WGS AF: 0.885 AC: 3080 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.58
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs972725; hg19: chr14-77748311;