chr1-16991570-T-C

Variant names:

• chr1-16991570-T-C
• rs2076604
• NM_022089.4:c.2251+164A>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 2P and 10B. PP3_Moderate BP6_Moderate BA1

The NM_022089.4(ATP13A2):​c.2251+164A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 152,114 control chromosomes in the GnomAD database, including 4,025 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.21 (4025 hom., cov: 33)
• Consequence: ATP13A2 NM_022089.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.06
• Publications: 13 publications found

Genes affected

ATP13A2 (HGNC:30213): (ATPase cation transporting 13A2) This gene encodes a member of the P5 subfamily of ATPases which transports inorganic cations as well as other substrates. Mutations in this gene are associated with Kufor-Rakeb syndrome (KRS), also referred to as Parkinson disease 9. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Nov 2008]

ATP13A2 Gene-Disease associations (from GenCC):

• Kufor-Rakeb syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, G2P, Illumina
• autosomal recessive spastic paraplegia type 78

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp
• parkinsonism due to ATP13A2 deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000226526 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
• BP6: Variant 1-16991570-T-C is Benign according to our data. Variant chr1-16991570-T-C is described in ClinVar as Benign. ClinVar VariationId is 1281617.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.549 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022089.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP13A2	NM_022089.4	MANE Select	c.2251+164A>G		intron	N/A	NP_071372.1	Q9NQ11-1
	ATP13A2	NM_001141973.3		c.2236+164A>G		intron	N/A	NP_001135445.1	Q9NQ11-3
	ATP13A2	NM_001141974.3		c.2236+164A>G		intron	N/A	NP_001135446.1	Q9NQ11-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP13A2	ENST00000326735.13	TSL:1 MANE Select	c.2251+164A>G		intron	N/A	ENSP00000327214.8	Q9NQ11-1
	ATP13A2	ENST00000452699.5	TSL:1	c.2236+164A>G		intron	N/A	ENSP00000413307.1	Q9NQ11-3
	ATP13A2	ENST00000341676.9	TSL:1	c.2236+164A>G		intron	N/A	ENSP00000341115.5	Q9NQ11-2

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32188 AN: 151996 Hom.: 4015 Cov.: 33

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.305

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.566

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.311

Gnomad MID AF: 0.232

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.228

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

GnomAD4 genome AF: 0.212 AC: 32220 AN: 152114 Hom.: 4025 Cov.: 33 AF XY: 0.222 AC XY: 16512 AN XY: 74372

African (AFR) AF: 0.147 AC: 6090 AN: 41502

American (AMR) AF: 0.305 AC: 4662 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 646 AN: 3470

East Asian (EAS) AF: 0.566 AC: 2931 AN: 5176

South Asian (SAS) AF: 0.240 AC: 1158 AN: 4830

European-Finnish (FIN) AF: 0.311 AC: 3282 AN: 10570

Middle Eastern (MID) AF: 0.229 AC: 67 AN: 292

European-Non Finnish (NFE) AF: 0.188 AC: 12758 AN: 67990

Other (OTH) AF: 0.227 AC: 480 AN: 2110

Alfa AF: 0.199 Hom.: 12495

Bravo AF: 0.211

Asia WGS AF: 0.362 AC: 1256 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Uncertain	23
DANN	Benign	0.53
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.94		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.94		Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2076604;

hg19: chr1-17318065;