14-77283714-T-G

Variant names:

• chr14-77283714-T-G
• rs2216089
• NM_013382.7:c.1653+83A>C

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.1653+83A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.532 in 1,177,070 control chromosomes in the GnomAD database, including 168,817 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.52 (21034 hom., cov: 32)
  • Exomes 𝑓: 0.53 (147783 hom.)
• Consequence: POMT2 NM_013382.7 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.77
• Publications: 8 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=-0.81).
• BP6: Variant 14-77283714-T-G is Benign according to our data. Variant chr14-77283714-T-G is described in ClinVar as Benign. ClinVar VariationId is 670967.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.551 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POMT2	NM_013382.7	MANE Select	c.1653+83A>C		intron	N/A	NP_037514.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POMT2	ENST00000261534.9	TSL:1 MANE Select	c.1653+83A>C		intron	N/A	ENSP00000261534.4
	POMT2	ENST00000682795.1		c.1653+83A>C		intron	N/A	ENSP00000507574.1
	POMT2	ENST00000682247.1		c.1653+83A>C		intron	N/A	ENSP00000507213.1

Frequencies

GnomAD3 genomes AF: 0.523 AC: 79393 AN: 151806 Hom.: 21016 Cov.: 32

Gnomad AFR AF: 0.485

Gnomad AMI AF: 0.572

Gnomad AMR AF: 0.454

Gnomad ASJ AF: 0.484

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.474

Gnomad FIN AF: 0.617

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.556

Gnomad OTH AF: 0.510

GnomAD4 exome AF: 0.534 AC: 546951 AN: 1025146 Hom.: 147783 AF XY: 0.532 AC XY: 281651 AN XY: 529048

African (AFR) AF: 0.482 AC: 12002 AN: 24886

American (AMR) AF: 0.387 AC: 17084 AN: 44120

Ashkenazi Jewish (ASJ) AF: 0.485 AC: 11361 AN: 23404

East Asian (EAS) AF: 0.486 AC: 18255 AN: 37590

South Asian (SAS) AF: 0.466 AC: 36032 AN: 77356

European-Finnish (FIN) AF: 0.609 AC: 32123 AN: 52730

Middle Eastern (MID) AF: 0.441 AC: 2058 AN: 4670

European-Non Finnish (NFE) AF: 0.552 AC: 394110 AN: 714222

Other (OTH) AF: 0.518 AC: 23926 AN: 46168

GnomAD4 genome AF: 0.523 AC: 79447 AN: 151924 Hom.: 21034 Cov.: 32 AF XY: 0.523 AC XY: 38834 AN XY: 74256

African (AFR) AF: 0.485 AC: 20067 AN: 41396

American (AMR) AF: 0.453 AC: 6919 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.484 AC: 1681 AN: 3470

East Asian (EAS) AF: 0.475 AC: 2448 AN: 5156

South Asian (SAS) AF: 0.474 AC: 2282 AN: 4810

European-Finnish (FIN) AF: 0.617 AC: 6516 AN: 10554

Middle Eastern (MID) AF: 0.483 AC: 141 AN: 292

European-Non Finnish (NFE) AF: 0.556 AC: 37788 AN: 67952

Other (OTH) AF: 0.515 AC: 1087 AN: 2112

Alfa AF: 0.536 Hom.: 58858

Bravo AF: 0.506

Asia WGS AF: 0.494 AC: 1716 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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.

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.082
DANN	Benign	0.34
PhyloP100		-1.8
PromoterAI		-0.0053	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: rs2216089; hg19: chr14-77750057; COSMIC: COSV55072374; COSMIC: COSV55072374;