rs438931

Variant names:

• chr14-77279967-G-A
• rs438931
• NM_013382.7:c.1786-39C>T

Your query was ambiguous. Multiple possible variants found:

• chr14-77279967-G-A
• chr14-77279967-G-T

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.1786-39C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 1,613,896 control chromosomes in the GnomAD database, including 16,685 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1419 hom., cov: 32)
  • Exomes 𝑓: 0.14 (15266 hom.)
• Consequence: POMT2 NM_013382.7 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.517
• Publications: 10 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=-0.82).
• BP6: Variant 14-77279967-G-A is Benign according to our data. Variant chr14-77279967-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 260297.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POMT2	NM_013382.7	c.1786-39C>T		intron_variant	Intron 17 of 20	ENST00000261534.9	NP_037514.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POMT2	ENST00000261534.9	c.1786-39C>T		intron_variant	Intron 17 of 20	1	NM_013382.7	ENSP00000261534.4

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19799 AN: 152028 Hom.: 1416 Cov.: 32

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.239

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.325

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.0925

Gnomad MID AF: 0.124

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.141

GnomAD2 exomes AF: 0.146 AC: 36673 AN: 251062 AF XY: 0.144

Gnomad AFR exome AF: 0.108

Gnomad AMR exome AF: 0.134

Gnomad ASJ exome AF: 0.168

Gnomad EAS exome AF: 0.345

Gnomad FIN exome AF: 0.0985

Gnomad NFE exome AF: 0.130

Gnomad OTH exome AF: 0.138

GnomAD4 exome AF: 0.138 AC: 202199 AN: 1461750 Hom.: 15266 Cov.: 35 AF XY: 0.138 AC XY: 100253 AN XY: 727170

African (AFR) AF: 0.107 AC: 3595 AN: 33480

American (AMR) AF: 0.142 AC: 6331 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 4382 AN: 26136

East Asian (EAS) AF: 0.341 AC: 13523 AN: 39686

South Asian (SAS) AF: 0.142 AC: 12270 AN: 86252

European-Finnish (FIN) AF: 0.0997 AC: 5322 AN: 53398

Middle Eastern (MID) AF: 0.129 AC: 743 AN: 5768

European-Non Finnish (NFE) AF: 0.132 AC: 147244 AN: 1111928

Other (OTH) AF: 0.146 AC: 8789 AN: 60390

GnomAD4 genome AF: 0.130 AC: 19812 AN: 152146 Hom.: 1419 Cov.: 32 AF XY: 0.131 AC XY: 9774 AN XY: 74372

African (AFR) AF: 0.106 AC: 4400 AN: 41504

American (AMR) AF: 0.152 AC: 2330 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 569 AN: 3472

East Asian (EAS) AF: 0.326 AC: 1680 AN: 5160

South Asian (SAS) AF: 0.143 AC: 688 AN: 4826

European-Finnish (FIN) AF: 0.0925 AC: 979 AN: 10580

Middle Eastern (MID) AF: 0.130 AC: 38 AN: 292

European-Non Finnish (NFE) AF: 0.127 AC: 8613 AN: 67984

Other (OTH) AF: 0.140 AC: 297 AN: 2114

Alfa AF: 0.135 Hom.: 2860

Bravo AF: 0.135

Asia WGS AF: 0.199 AC: 694 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 14, 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. -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.98
DANN	Benign	0.83
PhyloP100		-0.52
PromoterAI		0.018	Neutral
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: rs438931; hg19: chr14-77746310; COSMIC: COSV55070239; COSMIC: COSV55070239;