NM_013382.7:c.548-620A>C

Variant names:

• chr14-77303563-T-G
• rs8015231
• NM_013382.7:c.548-620A>C

Variant summary

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

The NM_013382.7(POMT2):​c.548-620A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 152,026 control chromosomes in the GnomAD database, including 1,126 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 0.11 (1126 hom., cov: 32)
• Consequence: POMT2 NM_013382.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.336
• Publications: 5 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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POMT2	NM_013382.7	c.548-620A>C		intron_variant	Intron 4 of 20	ENST00000261534.9	NP_037514.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POMT2	ENST00000261534.9	c.548-620A>C		intron_variant	Intron 4 of 20	1	NM_013382.7	ENSP00000261534.4

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17329 AN: 151908 Hom.: 1125 Cov.: 32

Gnomad AFR AF: 0.0837

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.337

Gnomad SAS AF: 0.0809

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.103

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

GnomAD4 genome AF: 0.114 AC: 17331 AN: 152026 Hom.: 1126 Cov.: 32 AF XY: 0.114 AC XY: 8476 AN XY: 74318

African (AFR) AF: 0.0838 AC: 3474 AN: 41462

American (AMR) AF: 0.104 AC: 1590 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 401 AN: 3468

East Asian (EAS) AF: 0.338 AC: 1736 AN: 5134

South Asian (SAS) AF: 0.0803 AC: 386 AN: 4806

European-Finnish (FIN) AF: 0.104 AC: 1101 AN: 10588

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.122 AC: 8291 AN: 67964

Other (OTH) AF: 0.102 AC: 215 AN: 2114

Alfa AF: 0.117 Hom.: 1455

Bravo AF: 0.116

Asia WGS AF: 0.193 AC: 669 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.82
DANN	Benign	0.71
PhyloP100		-0.34
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: rs8015231; hg19: chr14-77769906;