Variant chr6-145625446-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_005670.4(EPM2A):c.*1970T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0119 in 489,442 control chromosomes in the GnomAD database, including 52 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 13 hom., cov: 33)

Exomes 𝑓: 0.012 ( 39 hom. )

Consequence

EPM2A
NM_005670.4 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.562

Variant links:

Genes affected

EPM2A (HGNC:3413): (EPM2A glucan phosphatase, laforin) This gene encodes a dual-specificity phosphatase and may be involved in the regulation of glycogen metabolism. The protein acts on complex carbohydrates to prevent glycogen hyperphosphorylation, thus avoiding the formation of insoluble aggregates. Loss-of-function mutations in this gene have been associated with Lafora disease, a rare, adult-onset recessive neurodegenerative disease, which results in myoclonus epilepsy and usually results in death several years after the onset of symptoms. The disease is characterized by the accumulation of insoluble particles called Lafora bodies, which are derived from glycogen. [provided by RefSeq, Jan 2018]

EPM2A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 6-145625446-A-G is Benign according to our data. Variant chr6-145625446-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1197768.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-145625446-A-G is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0108 (1649/152344) while in subpopulation AMR AF= 0.0175 (268/15312). AF 95% confidence interval is 0.0158. There are 13 homozygotes in gnomad4. There are 766 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPM2A	NM_005670.4 linkuse as main transcript	c.*1970T>C		3_prime_UTR_variant	4/4	ENST00000367519.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPM2A	ENST00000367519.9 linkuse as main transcript	c.*1970T>C		3_prime_UTR_variant	4/4	1	NM_005670.4	P1	O95278-1

Frequencies

GnomAD3 genomes

AF:

0.0108

AC:

1641

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00697

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0175

Gnomad ASJ

AF:

0.00375

Gnomad EAS

AF:

0.00212

Gnomad SAS

AF:

0.0108

Gnomad FIN

AF:

0.00348

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0137

Gnomad OTH

AF:

0.0148

GnomAD4 exome

AF:

0.0124

AC:

4183

AN:

337098

Hom.:

Cov.:

AF XY:

0.0125

AC XY:

2215

AN XY:

177376

show subpopulations

Gnomad4 AFR exome

AF:

0.00887

Gnomad4 AMR exome

AF:

0.0183

Gnomad4 ASJ exome

AF:

0.00320

Gnomad4 EAS exome

AF:

0.00152

Gnomad4 SAS exome

AF:

0.0130

Gnomad4 FIN exome

AF:

0.00514

Gnomad4 NFE exome

AF:

0.0144

Gnomad4 OTH exome

AF:

0.0137

GnomAD4 genome

AF:

0.0108

AC:

1649

AN:

152344

Hom.:

Cov.:

AF XY:

0.0103

AC XY:

766

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.00712

Gnomad4 AMR

AF:

0.0175

Gnomad4 ASJ

AF:

0.00375

Gnomad4 EAS

AF:

0.00212

Gnomad4 SAS

AF:

0.0110

Gnomad4 FIN

AF:

0.00348

Gnomad4 NFE

AF:

0.0137

Gnomad4 OTH

AF:

0.0147

Alfa

AF:

0.0118

Hom.:

Bravo

AF:

0.0120

Asia WGS

AF:

0.0140

AC:

AN:

3472

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.13

DANN

Benign

0.54

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over