1-160130411-C-G

Variant names:

• chr1-160130411-C-G
• rs17846713
• NM_000702.4:c.1652-11C>G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000702.4(ATP1A2):​c.1652-11C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0451 in 1,614,142 control chromosomes in the GnomAD database, including 1,979 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.032 (135 hom., cov: 32)
  • Exomes 𝑓: 0.046 (1844 hom.)
• Consequence: ATP1A2 NM_000702.4 intron
• Scores: Splicing: ADA: 0.0006314
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:13
• Conservation: PhyloP100: -0.339

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 1-160130411-C-G is Benign according to our data. Variant chr1-160130411-C-G is described in ClinVar as [Benign]. Clinvar id is 256763.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-160130411-C-G is described in Lovd as [Benign]. Variant chr1-160130411-C-G is described in Lovd as [Likely_benign].
• BA1: GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.053 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP1A2	NM_000702.4	c.1652-11C>G		intron_variant	Intron 12 of 22	ENST00000361216.8	NP_000693.1
ATP1A2	XM_047421286.1	c.761-11C>G		intron_variant	Intron 5 of 15		XP_047277242.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP1A2	ENST00000361216.8	c.1652-11C>G		intron_variant	Intron 12 of 22	1	NM_000702.4	ENSP00000354490.3
ATP1A2	ENST00000392233.7	c.1652-11C>G		intron_variant	Intron 12 of 22	5		ENSP00000376066.3
ATP1A2	ENST00000447527.1	c.782-11C>G		intron_variant	Intron 5 of 15	2		ENSP00000411705.1
ATP1A2	ENST00000472488.5	n.1755-11C>G		intron_variant	Intron 12 of 19	2

Frequencies

GnomAD3 genomes AF: 0.0325 AC: 4949 AN: 152166 Hom.: 135 Cov.: 32

Gnomad AFR AF: 0.00893

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0295

Gnomad ASJ AF: 0.0297

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0164

Gnomad FIN AF: 0.0352

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0513

Gnomad OTH AF: 0.0278

GnomAD3 exomes AF: 0.0324 AC: 8156 AN: 251394 Hom.: 196 AF XY: 0.0336 AC XY: 4570 AN XY: 135878

Gnomad AFR exome AF: 0.00775

Gnomad AMR exome AF: 0.0149

Gnomad ASJ exome AF: 0.0306

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0219

Gnomad FIN exome AF: 0.0381

Gnomad NFE exome AF: 0.0483

Gnomad OTH exome AF: 0.0362

GnomAD4 exome AF: 0.0464 AC: 67816 AN: 1461858 Hom.: 1844 Cov.: 33 AF XY: 0.0457 AC XY: 33202 AN XY: 727230

Gnomad4 AFR exome AF: 0.00669

Gnomad4 AMR exome AF: 0.0164

Gnomad4 ASJ exome AF: 0.0312

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.0217

Gnomad4 FIN exome AF: 0.0408

Gnomad4 NFE exome AF: 0.0534

Gnomad4 OTH exome AF: 0.0415

GnomAD4 genome AF: 0.0325 AC: 4947 AN: 152284 Hom.: 135 Cov.: 32 AF XY: 0.0306 AC XY: 2275 AN XY: 74466

Gnomad4 AFR AF: 0.00890

Gnomad4 AMR AF: 0.0295

Gnomad4 ASJ AF: 0.0297

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0164

Gnomad4 FIN AF: 0.0352

Gnomad4 NFE AF: 0.0513

Gnomad4 OTH AF: 0.0275

Alfa AF: 0.0389 Hom.: 35

Bravo AF: 0.0324

Asia WGS AF: 0.00722 AC: 26 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:13

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

-

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:3

-

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Migraine, familial hemiplegic, 2 Benign:2

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Alternating hemiplegia of childhood 1 Benign:2

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Fetal akinesia, respiratory insufficiency, microcephaly, polymicrogyria, and dysmorphic facies Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Developmental and epileptic encephalopathy 98 Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Familial hemiplegic migraine Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	1.2
DANN	Benign	0.70

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00063
dbscSNV1_RF	Benign	0.026
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: rs17846713; hg19: chr1-160100201;