rs1023421

Positions:

• chr1-160124854-A-G
• chr1-160124854-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000702.4(ATP1A2):​c.631-282A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.572 in 152,078 control chromosomes in the GnomAD database, including 25,494 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.57 (25494 hom., cov: 32)
• Consequence: ATP1A2 NM_000702.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.26

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 1-160124854-A-G is Benign according to our data. Variant chr1-160124854-A-G is described in ClinVar as [Benign]. Clinvar id is 668018.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.716 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP1A2	NM_000702.4	c.631-282A>G		intron_variant		ENST00000361216.8	NP_000693.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP1A2	ENST00000361216.8	c.631-282A>G		intron_variant		1	NM_000702.4	ENSP00000354490	P1
ATP1A2	ENST00000392233.7	c.631-282A>G		intron_variant		5		ENSP00000376066
ATP1A2	ENST00000468587.1	n.235-282A>G		intron_variant, non_coding_transcript_variant		2
ATP1A2	ENST00000472488.5	n.734-282A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.572 AC: 86873 AN: 151960 Hom.: 25492 Cov.: 32

Gnomad AFR AF: 0.453

Gnomad AMI AF: 0.652

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.596

Gnomad EAS AF: 0.528

Gnomad SAS AF: 0.737

Gnomad FIN AF: 0.649

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.632

Gnomad OTH AF: 0.557

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.572 AC: 86921 AN: 152078 Hom.: 25494 Cov.: 32 AF XY: 0.573 AC XY: 42600 AN XY: 74356

Gnomad4 AFR AF: 0.453

Gnomad4 AMR AF: 0.526

Gnomad4 ASJ AF: 0.596

Gnomad4 EAS AF: 0.529

Gnomad4 SAS AF: 0.736

Gnomad4 FIN AF: 0.649

Gnomad4 NFE AF: 0.632

Gnomad4 OTH AF: 0.554

Alfa AF: 0.619 Hom.: 57520

Bravo AF: 0.551

Asia WGS AF: 0.595 AC: 2070 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2018

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.62
DANN	Benign	0.72

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

Other links and lift over

dbSNP: rs1023421; hg19: chr1-160094644;