rs3783986

Variant names:

• chr14-77296529-C-T
• rs3783986
• NM_013382.7:c.1007-256G>A

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.1007-256G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.419 in 519,272 control chromosomes in the GnomAD database, including 46,553 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.41 (13190 hom., cov: 32)
  • Exomes 𝑓: 0.42 (33363 hom.)
• Consequence: POMT2 NM_013382.7 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.243
• Publications: 4 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 14-77296529-C-T is Benign according to our data. Variant chr14-77296529-C-T is described in ClinVar as Benign. ClinVar VariationId is 683960.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POMT2	NM_013382.7	c.1007-256G>A		intron_variant	Intron 8 of 20	ENST00000261534.9	NP_037514.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POMT2	ENST00000261534.9	c.1007-256G>A		intron_variant	Intron 8 of 20	1	NM_013382.7	ENSP00000261534.4

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62876 AN: 151958 Hom.: 13181 Cov.: 32

Gnomad AFR AF: 0.454

Gnomad AMI AF: 0.398

Gnomad AMR AF: 0.438

Gnomad ASJ AF: 0.494

Gnomad EAS AF: 0.503

Gnomad SAS AF: 0.522

Gnomad FIN AF: 0.339

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.376

Gnomad OTH AF: 0.436

GnomAD4 exome AF: 0.422 AC: 154899 AN: 367196 Hom.: 33363 Cov.: 0 AF XY: 0.428 AC XY: 82243 AN XY: 191940

African (AFR) AF: 0.460 AC: 5050 AN: 10968

American (AMR) AF: 0.481 AC: 7311 AN: 15202

Ashkenazi Jewish (ASJ) AF: 0.503 AC: 5854 AN: 11628

East Asian (EAS) AF: 0.504 AC: 12580 AN: 24946

South Asian (SAS) AF: 0.538 AC: 21551 AN: 40038

European-Finnish (FIN) AF: 0.342 AC: 7808 AN: 22862

Middle Eastern (MID) AF: 0.511 AC: 840 AN: 1644

European-Non Finnish (NFE) AF: 0.388 AC: 84730 AN: 218278

Other (OTH) AF: 0.424 AC: 9175 AN: 21630

GnomAD4 genome AF: 0.414 AC: 62928 AN: 152076 Hom.: 13190 Cov.: 32 AF XY: 0.417 AC XY: 30997 AN XY: 74332

African (AFR) AF: 0.454 AC: 18839 AN: 41460

American (AMR) AF: 0.438 AC: 6695 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.494 AC: 1713 AN: 3468

East Asian (EAS) AF: 0.502 AC: 2592 AN: 5160

South Asian (SAS) AF: 0.522 AC: 2518 AN: 4828

European-Finnish (FIN) AF: 0.339 AC: 3582 AN: 10568

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.376 AC: 25576 AN: 67976

Other (OTH) AF: 0.433 AC: 915 AN: 2114

Alfa AF: 0.400 Hom.: 20961

Bravo AF: 0.424

Asia WGS AF: 0.520 AC: 1813 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 19, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	-0.96
CADD	Benign	0.81
DANN	Benign	0.75
PhyloP100		0.24
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: rs3783986; hg19: chr14-77762872;