chr1-160139013-C-T

Position:

• chr1-160139013-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000702.4(ATP1A2):​c.2841-627C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 152,246 control chromosomes in the GnomAD database, including 1,051 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.10 (1051 hom., cov: 32)
• Consequence: ATP1A2 NM_000702.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.293

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP1A2	NM_000702.4	c.2841-627C>T		intron_variant		ENST00000361216.8	NP_000693.1
ATP1A2	XM_047421286.1	c.1950-627C>T		intron_variant			XP_047277242.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP1A2	ENST00000361216.8	c.2841-627C>T		intron_variant		1	NM_000702.4	ENSP00000354490	P1
ATP1A2	ENST00000392233.7	c.2841-627C>T		intron_variant		5		ENSP00000376066
ATP1A2	ENST00000447527.1	c.1922-627C>T		intron_variant		2		ENSP00000411705
ATP1A2	ENST00000463989.1	n.177-627C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15365 AN: 152128 Hom.: 1049 Cov.: 32

Gnomad AFR AF: 0.0233

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.0633

Gnomad SAS AF: 0.0959

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.105

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

GnomAD4 genome AF: 0.101 AC: 15373 AN: 152246 Hom.: 1051 Cov.: 32 AF XY: 0.103 AC XY: 7681 AN XY: 74436

Gnomad4 AFR AF: 0.0232

Gnomad4 AMR AF: 0.125

Gnomad4 ASJ AF: 0.101

Gnomad4 EAS AF: 0.0632

Gnomad4 SAS AF: 0.0954

Gnomad4 FIN AF: 0.185

Gnomad4 NFE AF: 0.133

Gnomad4 OTH AF: 0.106

Alfa AF: 0.123 Hom.: 1609

Bravo AF: 0.0902

Asia WGS AF: 0.0870 AC: 304 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.93
DANN	Benign	0.36

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: rs12410866; hg19: chr1-160108803;