rs2076600

Variant names:

• chr1-17010896-G-A
• rs2076600
• NM_022089.4:c.10+833C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-17010896-G-A
• chr1-17010896-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022089.4(ATP13A2):​c.10+833C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 151,938 control chromosomes in the GnomAD database, including 8,832 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 0.33 (8832 hom., cov: 31)
• Consequence: ATP13A2 NM_022089.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.704
• Publications: 14 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: Labcorp Genetics (formerly Invitae), Illumina, Genomics England PanelApp, G2P, ClinGen
• autosomal recessive spastic paraplegia type 78

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

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000288636 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.528 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP13A2	NM_022089.4	c.10+833C>T		intron_variant	Intron 1 of 28	ENST00000326735.13	NP_071372.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP13A2	ENST00000326735.13	c.10+833C>T		intron_variant	Intron 1 of 28	1	NM_022089.4	ENSP00000327214.8
ATP13A2	ENST00000452699.5	c.10+833C>T		intron_variant	Intron 1 of 28	1		ENSP00000413307.1
ATP13A2	ENST00000341676.9	c.10+833C>T		intron_variant	Intron 1 of 26	1		ENSP00000341115.5
ENSG00000288636	ENST00000617114.5	c.29+833C>T		intron_variant	Intron 1 of 3	5		ENSP00000478781.2

Frequencies

GnomAD3 genomes AF: 0.331 AC: 50281 AN: 151820 Hom.: 8814 Cov.: 31

Gnomad AFR AF: 0.414

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.544

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.334

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.328

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

GnomAD4 genome AF: 0.331 AC: 50340 AN: 151938 Hom.: 8832 Cov.: 31 AF XY: 0.337 AC XY: 25045 AN XY: 74254

African (AFR) AF: 0.414 AC: 17152 AN: 41434

American (AMR) AF: 0.393 AC: 6001 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.303 AC: 1051 AN: 3470

East Asian (EAS) AF: 0.545 AC: 2800 AN: 5140

South Asian (SAS) AF: 0.304 AC: 1460 AN: 4810

European-Finnish (FIN) AF: 0.318 AC: 3361 AN: 10560

Middle Eastern (MID) AF: 0.332 AC: 97 AN: 292

European-Non Finnish (NFE) AF: 0.257 AC: 17462 AN: 67934

Other (OTH) AF: 0.326 AC: 687 AN: 2108

Alfa AF: 0.293 Hom.: 15633

Bravo AF: 0.342

Asia WGS AF: 0.388 AC: 1350 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.5
DANN	Benign	0.90
PhyloP100		-0.70
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2076600; hg19: chr1-17337391;