Variant rs1046995 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000702.4(ATP1A2):c.*1629T>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 0.217 in 152,198 control chromosomes in the GnomAD database, including 3,673 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 3673 hom., cov: 32)

Exomes 𝑓: 0.18 ( 0 hom. )

Consequence

ATP1A2
NM_000702.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0140

Variant links:

Genes affected

ATP1A2 (HGNC:800): (ATPase Na+/K+ transporting subunit alpha 2) The protein encoded by this gene belongs to the family of P-type cation transport ATPases, and to the subfamily of Na+/K+ -ATPases. Na+/K+ -ATPase is an integral membrane protein responsible for establishing and maintaining the electrochemical gradients of Na and K ions across the plasma membrane. These gradients are essential for osmoregulation, for sodium-coupled transport of a variety of organic and inorganic molecules, and for electrical excitability of nerve and muscle. This enzyme is composed of two subunits, a large catalytic subunit (alpha) and a smaller glycoprotein subunit (beta). The catalytic subunit of Na+/K+ -ATPase is encoded by multiple genes. This gene encodes an alpha 2 subunit. Mutations in this gene result in familial basilar or hemiplegic migraines, and in a rare syndrome known as alternating hemiplegia of childhood. [provided by RefSeq, Oct 2008]

ATP1A2 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=-0.84).

BP6

Variant 1-160142951-T-C is Benign according to our data. Variant chr1-160142951-T-C is described in ClinVar as [Benign]. Clinvar id is 293179.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP1A2	NM_000702.4 linkuse as main transcript	c.*1629T>C		3_prime_UTR_variant	23/23	ENST00000361216.8	NP_000693.1	P50993A0A0S2Z3W6
ATP1A2	XM_047421286.1 linkuse as main transcript	c.*1629T>C		3_prime_UTR_variant	16/16		XP_047277242.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP1A2	ENST00000361216.8 linkuse as main transcript	c.*1629T>C		3_prime_UTR_variant	23/23	1	NM_000702.4	ENSP00000354490.3		P50993
ATP1A2	ENST00000447527.1 linkuse as main transcript	c.*1629T>C		3_prime_UTR_variant	16/16	2		ENSP00000411705.1		H0Y7C1

Frequencies

GnomAD3 genomes

AF:

0.217

AC:

33043

AN:

152060

Hom.:

3674

Cov.:

show subpopulations

Gnomad AFR

AF:

0.253

Gnomad AMI

AF:

0.261

Gnomad AMR

AF:

0.161

Gnomad ASJ

AF:

0.206

Gnomad EAS

AF:

0.155

Gnomad SAS

AF:

0.283

Gnomad FIN

AF:

0.152

Gnomad MID

AF:

0.171

Gnomad NFE

AF:

0.219

Gnomad OTH

AF:

0.218

GnomAD4 exome

AF:

0.182

AC:

AN:

Hom.:

Cov.:

AF XY:

0.214

AC XY:

AN XY:

show subpopulations

Gnomad4 ASJ exome

AF:

0.500

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.167

GnomAD4 genome

AF:

0.217

AC:

33043

AN:

152176

Hom.:

3673

Cov.:

AF XY:

0.214

AC XY:

15926

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.252

Gnomad4 AMR

AF:

0.161

Gnomad4 ASJ

AF:

0.206

Gnomad4 EAS

AF:

0.155

Gnomad4 SAS

AF:

0.282

Gnomad4 FIN

AF:

0.152

Gnomad4 NFE

AF:

0.219

Gnomad4 OTH

AF:

0.216

Alfa

AF:

0.213

Hom.:

4395

Bravo

AF:

0.216

Asia WGS

AF:

0.209

AC:

726

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Migraine, familial hemiplegic, 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Alternating hemiplegia of childhood 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.3

DANN

Benign

0.69

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