NM_013382.7:c.1383G>A

Variant names:

• chr14-77285582-C-T
• rs2270419
• NM_013382.7:c.1383G>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_013382.7(POMT2):​c.1383G>A​(p.Arg461Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.807 in 1,613,592 control chromosomes in the GnomAD database, including 526,782 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.83 (52375 hom., cov: 31)
  • Exomes 𝑓: 0.80 (474407 hom.)
• Consequence: POMT2 NM_013382.7 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: 0.0250
• Publications: 27 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: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P
• 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP6: Variant 14-77285582-C-T is Benign according to our data. Variant chr14-77285582-C-T is described in ClinVar as Benign. ClinVar VariationId is 166906.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.025 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.929 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013382.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POMT2	NM_013382.7	MANE Select	c.1383G>A	p.Arg461Arg	synonymous	Exon 13 of 21	NP_037514.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POMT2	ENST00000261534.9	TSL:1 MANE Select	c.1383G>A	p.Arg461Arg	synonymous	Exon 13 of 21	ENSP00000261534.4	Q9UKY4-1
	POMT2	ENST00000682795.1		c.1383G>A	p.Arg461Arg	synonymous	Exon 13 of 22	ENSP00000507574.1	A0A804HJN3
	POMT2	ENST00000923942.1		c.1383G>A	p.Arg461Arg	synonymous	Exon 13 of 22	ENSP00000594001.1

Frequencies

GnomAD3 genomes AF: 0.829 AC: 125885 AN: 151936 Hom.: 52327 Cov.: 31

Gnomad AFR AF: 0.868

Gnomad AMI AF: 0.850

Gnomad AMR AF: 0.762

Gnomad ASJ AF: 0.855

Gnomad EAS AF: 0.951

Gnomad SAS AF: 0.804

Gnomad FIN AF: 0.856

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.806

Gnomad OTH AF: 0.838

GnomAD2 exomes AF: 0.818 AC: 205702 AN: 251466 AF XY: 0.818

Gnomad AFR exome AF: 0.875

Gnomad AMR exome AF: 0.734

Gnomad ASJ exome AF: 0.848

Gnomad EAS exome AF: 0.963

Gnomad FIN exome AF: 0.844

Gnomad NFE exome AF: 0.809

Gnomad OTH exome AF: 0.815

GnomAD4 exome AF: 0.805 AC: 1176143 AN: 1461538 Hom.: 474407 Cov.: 65 AF XY: 0.805 AC XY: 585076 AN XY: 727094

African (AFR) AF: 0.874 AC: 29243 AN: 33472

American (AMR) AF: 0.744 AC: 33289 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.852 AC: 22257 AN: 26134

East Asian (EAS) AF: 0.967 AC: 38374 AN: 39698

South Asian (SAS) AF: 0.795 AC: 68594 AN: 86254

European-Finnish (FIN) AF: 0.842 AC: 44970 AN: 53418

Middle Eastern (MID) AF: 0.800 AC: 4616 AN: 5768

European-Non Finnish (NFE) AF: 0.797 AC: 885592 AN: 1111678

Other (OTH) AF: 0.815 AC: 49208 AN: 60394

GnomAD4 genome AF: 0.829 AC: 125986 AN: 152054 Hom.: 52375 Cov.: 31 AF XY: 0.830 AC XY: 61685 AN XY: 74322

African (AFR) AF: 0.868 AC: 36009 AN: 41472

American (AMR) AF: 0.762 AC: 11632 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.855 AC: 2968 AN: 3470

East Asian (EAS) AF: 0.951 AC: 4904 AN: 5154

South Asian (SAS) AF: 0.804 AC: 3870 AN: 4814

European-Finnish (FIN) AF: 0.856 AC: 9032 AN: 10556

Middle Eastern (MID) AF: 0.762 AC: 224 AN: 294

European-Non Finnish (NFE) AF: 0.806 AC: 54798 AN: 67998

Other (OTH) AF: 0.841 AC: 1777 AN: 2114

Alfa AF: 0.813 Hom.: 79296

Bravo AF: 0.825

Asia WGS AF: 0.886 AC: 3082 AN: 3478

EpiCase AF: 0.805

EpiControl AF: 0.806

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	1	Autosomal recessive limb-girdle muscular dystrophy type 2N (1)
-	-	1	Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A2 (1)
-	-	1	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 (1)
-	-	1	Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B2 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	12
DANN	Benign	0.83
PhyloP100		0.025
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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: rs2270419; hg19: chr14-77751925; COSMIC: COSV55070424; COSMIC: COSV55070424;