NM_013382.7:c.1184-47A>C

Variant names:

• chr14-77288878-T-G
• rs2287387
• NM_013382.7:c.1184-47A>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_013382.7(POMT2):​c.1184-47A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.53 in 1,526,204 control chromosomes in the GnomAD database, including 217,298 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.51 (20408 hom., cov: 29)
  • Exomes 𝑓: 0.53 (196890 hom.)
• Consequence: POMT2 NM_013382.7 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.827
• Publications: 7 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: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 14-77288878-T-G is Benign according to our data. Variant chr14-77288878-T-G is described in ClinVar as Benign. ClinVar VariationId is 260290.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013382.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POMT2	NM_013382.7	MANE Select	c.1184-47A>C		intron	N/A	NP_037514.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POMT2	ENST00000261534.9	TSL:1 MANE Select	c.1184-47A>C		intron	N/A	ENSP00000261534.4	Q9UKY4-1
	POMT2	ENST00000682795.1		c.1184-47A>C		intron	N/A	ENSP00000507574.1	A0A804HJN3
	POMT2	ENST00000923942.1		c.1184-47A>C		intron	N/A	ENSP00000594001.1

Frequencies

GnomAD3 genomes AF: 0.515 AC: 77948 AN: 151408 Hom.: 20390 Cov.: 29

Gnomad AFR AF: 0.480

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.397

Gnomad ASJ AF: 0.485

Gnomad EAS AF: 0.456

Gnomad SAS AF: 0.474

Gnomad FIN AF: 0.616

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.555

Gnomad OTH AF: 0.500

GnomAD2 exomes AF: 0.499 AC: 124783 AN: 249944 AF XY: 0.506

Gnomad AFR exome AF: 0.484

Gnomad AMR exome AF: 0.313

Gnomad ASJ exome AF: 0.475

Gnomad EAS exome AF: 0.458

Gnomad FIN exome AF: 0.615

Gnomad NFE exome AF: 0.554

Gnomad OTH exome AF: 0.507

GnomAD4 exome AF: 0.531 AC: 730333 AN: 1374678 Hom.: 196890 Cov.: 20 AF XY: 0.531 AC XY: 365598 AN XY: 689012

African (AFR) AF: 0.479 AC: 15154 AN: 31656

American (AMR) AF: 0.321 AC: 14277 AN: 44510

Ashkenazi Jewish (ASJ) AF: 0.485 AC: 12378 AN: 25544

East Asian (EAS) AF: 0.470 AC: 18445 AN: 39206

South Asian (SAS) AF: 0.465 AC: 39227 AN: 84346

European-Finnish (FIN) AF: 0.608 AC: 32226 AN: 52978

Middle Eastern (MID) AF: 0.445 AC: 2493 AN: 5608

European-Non Finnish (NFE) AF: 0.548 AC: 566441 AN: 1033326

Other (OTH) AF: 0.516 AC: 29692 AN: 57504

GnomAD4 genome AF: 0.515 AC: 78004 AN: 151526 Hom.: 20408 Cov.: 29 AF XY: 0.514 AC XY: 38021 AN XY: 74024

African (AFR) AF: 0.480 AC: 19808 AN: 41240

American (AMR) AF: 0.396 AC: 6035 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.485 AC: 1683 AN: 3470

East Asian (EAS) AF: 0.457 AC: 2339 AN: 5118

South Asian (SAS) AF: 0.475 AC: 2280 AN: 4804

European-Finnish (FIN) AF: 0.616 AC: 6441 AN: 10458

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.555 AC: 37701 AN: 67898

Other (OTH) AF: 0.504 AC: 1059 AN: 2100

Alfa AF: 0.537 Hom.: 5621

Bravo AF: 0.494

Asia WGS AF: 0.486 AC: 1691 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Autosomal recessive limb-girdle muscular dystrophy type 2N (1)
-	-	1	Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A2 (1)
-	-	1	Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B2 (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.20
DANN	Benign	0.55
PhyloP100		-0.83
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: rs2287387; hg19: chr14-77755221; COSMIC: COSV55070251; COSMIC: COSV55070251;