rs1555354172

Variant names:

• chr14-77301193-C-A
• rs1555354172
• NM_013382.7:c.713G>T

Your query was ambiguous. Multiple possible variants found:

• chr14-77301193-C-A
• chr14-77301193-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PM2 PP3_Moderate PP5

The NM_013382.7(POMT2):​c.713G>T​(p.Gly238Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: POMT2 NM_013382.7 missense
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:1 U:1
• Conservation: PhyloP100: 6.08
• Publications: 0 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: Uncertain_significance. The variant received 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.873
• PP5: Variant 14-77301193-C-A is Pathogenic according to our data. Variant chr14-77301193-C-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 436381.We mark this variant Likely_pathogenic, oryginal submission is: [Conflicting_classifications_of_pathogenicity].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POMT2	NM_013382.7	c.713G>T	p.Gly238Val	missense_variant	Exon 6 of 21	ENST00000261534.9	NP_037514.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POMT2	ENST00000261534.9	c.713G>T	p.Gly238Val	missense_variant	Exon 6 of 21	1	NM_013382.7	ENSP00000261534.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Pathogenic:1 Uncertain:1

Revision: criteria provided, conflicting classifications

Submissions by phenotype

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

Nov 16, 2020

Kariminejad - Najmabadi Pathology & Genetics Center

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

[PM1, PM2, PP3, PP5] -

not specified Uncertain:1

Aug 04, 2016

Genetic Services Laboratory, University of Chicago

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.20
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.96	D
M_CAP	Uncertain	0.13	D
MetaRNN	Pathogenic	0.87	D
MetaSVM	Uncertain	0.51	D
MutationAssessor	Benign	1.6	L
PhyloP100		6.1
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.57	N
REVEL	Pathogenic	0.86
Sift	Benign	0.12	T
Sift4G	Benign	0.13	T
Polyphen		0.98	D
Vest4		0.94
MutPred		0.62		Gain of catalytic residue at V242 (P = 0);
MVP		0.94
MPC		0.34
ClinPred		0.93	D
GERP RS		4.9
PromoterAI		0.020	Neutral
Varity_R		0.60
gMVP		0.75
Mutation Taster		=7/93	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.29		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.29		Position offset: -9

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1555354172; hg19: chr14-77767536;