rs2270420

Variant names:

• chr14-77320520-C-A
• rs2270420
• NM_013382.7:c.162G>T

Your query was ambiguous. Multiple possible variants found:

• chr14-77320520-C-A
• chr14-77320520-C-G
• chr14-77320520-C-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_013382.7(POMT2):​c.162G>T​(p.Ala54Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0673 in 1,553,826 control chromosomes in the GnomAD database, including 4,377 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. A54A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.058 (390 hom., cov: 32)
  • Exomes 𝑓: 0.068 (3987 hom.)
• Consequence: POMT2 NM_013382.7 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:12
• Conservation: PhyloP100: 0.256
• 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 14-77320520-C-A is Benign according to our data. Variant chr14-77320520-C-A is described in ClinVar as Benign. ClinVar VariationId is 95536.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.256 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POMT2	NM_013382.7	c.162G>T	p.Ala54Ala	synonymous_variant	Exon 1 of 21	ENST00000261534.9	NP_037514.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POMT2	ENST00000261534.9	c.162G>T	p.Ala54Ala	synonymous_variant	Exon 1 of 21	1	NM_013382.7	ENSP00000261534.4

Frequencies

GnomAD3 genomes AF: 0.0579 AC: 8814 AN: 152188 Hom.: 391 Cov.: 32

Gnomad AFR AF: 0.0117

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.0453

Gnomad ASJ AF: 0.0614

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.0746

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0657

Gnomad OTH AF: 0.0760

GnomAD2 exomes AF: 0.0744 AC: 11562 AN: 155460 AF XY: 0.0752

Gnomad AFR exome AF: 0.0106

Gnomad AMR exome AF: 0.0326

Gnomad ASJ exome AF: 0.0667

Gnomad EAS exome AF: 0.242

Gnomad FIN exome AF: 0.119

Gnomad NFE exome AF: 0.0642

Gnomad OTH exome AF: 0.0662

GnomAD4 exome AF: 0.0684 AC: 95795 AN: 1401520 Hom.: 3987 Cov.: 31 AF XY: 0.0687 AC XY: 47624 AN XY: 693278

African (AFR) AF: 0.00922 AC: 297 AN: 32202

American (AMR) AF: 0.0351 AC: 1335 AN: 37990

Ashkenazi Jewish (ASJ) AF: 0.0647 AC: 1638 AN: 25314

East Asian (EAS) AF: 0.223 AC: 8164 AN: 36540

South Asian (SAS) AF: 0.0717 AC: 5788 AN: 80690

European-Finnish (FIN) AF: 0.111 AC: 4276 AN: 38374

Middle Eastern (MID) AF: 0.0494 AC: 282 AN: 5706

European-Non Finnish (NFE) AF: 0.0642 AC: 69780 AN: 1086274

Other (OTH) AF: 0.0725 AC: 4235 AN: 58430

GnomAD4 genome AF: 0.0578 AC: 8805 AN: 152306 Hom.: 390 Cov.: 32 AF XY: 0.0614 AC XY: 4576 AN XY: 74474

African (AFR) AF: 0.0117 AC: 485 AN: 41580

American (AMR) AF: 0.0452 AC: 692 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0614 AC: 213 AN: 3470

East Asian (EAS) AF: 0.221 AC: 1142 AN: 5168

South Asian (SAS) AF: 0.0741 AC: 358 AN: 4832

European-Finnish (FIN) AF: 0.114 AC: 1211 AN: 10624

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0657 AC: 4467 AN: 68004

Other (OTH) AF: 0.0752 AC: 159 AN: 2114

Alfa AF: 0.0640 Hom.: 483

Bravo AF: 0.0527

Asia WGS AF: 0.112 AC: 391 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:8

-

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jan 13, 2015

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

p.Ala54Ala in exon 1 of POMT2: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. It has been identified in 5.8% (478/8280) of European American chromosomes from a broad population by the NHLBI Exome Sequenc ing Project (http://evs.gs.washington.edu/EVS; dbSNP rs2270420). -

-

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Oct 25, 2012

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Jul 26, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:2

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A2;C3150416:Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B2;C3150418:Autosomal recessive limb-girdle muscular dystrophy type 2N Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autosomal recessive limb-girdle muscular dystrophy type 2N Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	5.8
DANN	Benign	0.66
PhyloP100		0.26
PromoterAI		-0.019	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: rs2270420; hg19: chr14-77786863; COSMIC: COSV53623081; COSMIC: COSV53623081;