rs61990292

Variant names:

• chr14-77279774-G-A
• rs61990292
• NM_013382.7:c.1891+49C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4 BP6_Very_Strong BA1

The NM_013382.7(POMT2):​c.1891+49C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0569 in 1,567,636 control chromosomes in the GnomAD database, including 3,034 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.042 (208 hom., cov: 32)
  • Exomes 𝑓: 0.059 (2826 hom.)
• Consequence: POMT2 NM_013382.7 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.50
• Publications: 2 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.184).
• BP6: Variant 14-77279774-G-A is Benign according to our data. Variant chr14-77279774-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 260298.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0631 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POMT2	NM_013382.7	c.1891+49C>T		intron_variant	Intron 18 of 20	ENST00000261534.9	NP_037514.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POMT2	ENST00000261534.9	c.1891+49C>T		intron_variant	Intron 18 of 20	1	NM_013382.7	ENSP00000261534.4

Frequencies

GnomAD3 genomes AF: 0.0418 AC: 6361 AN: 152066 Hom.: 208 Cov.: 32

Gnomad AFR AF: 0.0115

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.0354

Gnomad ASJ AF: 0.0311

Gnomad EAS AF: 0.000968

Gnomad SAS AF: 0.00849

Gnomad FIN AF: 0.0501

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0647

Gnomad OTH AF: 0.0402

GnomAD2 exomes AF: 0.0414 AC: 8002 AN: 193232 AF XY: 0.0410

Gnomad AFR exome AF: 0.0104

Gnomad AMR exome AF: 0.0268

Gnomad ASJ exome AF: 0.0279

Gnomad EAS exome AF: 0.000138

Gnomad FIN exome AF: 0.0465

Gnomad NFE exome AF: 0.0684

Gnomad OTH exome AF: 0.0436

GnomAD4 exome AF: 0.0585 AC: 82813 AN: 1415452 Hom.: 2826 Cov.: 30 AF XY: 0.0571 AC XY: 40141 AN XY: 702542

African (AFR) AF: 0.00913 AC: 297 AN: 32522

American (AMR) AF: 0.0286 AC: 1137 AN: 39822

Ashkenazi Jewish (ASJ) AF: 0.0267 AC: 677 AN: 25394

East Asian (EAS) AF: 0.000211 AC: 8 AN: 37926

South Asian (SAS) AF: 0.0110 AC: 906 AN: 82570

European-Finnish (FIN) AF: 0.0432 AC: 2009 AN: 46520

Middle Eastern (MID) AF: 0.0269 AC: 154 AN: 5722

European-Non Finnish (NFE) AF: 0.0690 AC: 74900 AN: 1086010

Other (OTH) AF: 0.0462 AC: 2725 AN: 58966

GnomAD4 genome AF: 0.0418 AC: 6361 AN: 152184 Hom.: 208 Cov.: 32 AF XY: 0.0412 AC XY: 3063 AN XY: 74418

African (AFR) AF: 0.0115 AC: 477 AN: 41522

American (AMR) AF: 0.0354 AC: 541 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0311 AC: 108 AN: 3470

East Asian (EAS) AF: 0.000970 AC: 5 AN: 5152

South Asian (SAS) AF: 0.00850 AC: 41 AN: 4824

European-Finnish (FIN) AF: 0.0501 AC: 532 AN: 10612

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0647 AC: 4396 AN: 67988

Other (OTH) AF: 0.0398 AC: 84 AN: 2110

Alfa AF: 0.0490 Hom.: 67

Bravo AF: 0.0402

Asia WGS AF: 0.00606 AC: 22 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Feb 01, 2017

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:2

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. -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.4
DANN	Benign	0.88
PhyloP100		1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs61990292; hg19: chr14-77746117;