rs2871776

Positions:

• chr1-17001806-T-C

Variant summary

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

The NM_022089.4(ATP13A2):​c.705+228A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.561 in 152,086 control chromosomes in the GnomAD database, including 24,940 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.56 (24940 hom., cov: 33)
• Consequence: ATP13A2 NM_022089.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.238

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 1-17001806-T-C is Benign according to our data. Variant chr1-17001806-T-C is described in ClinVar as [Benign]. Clinvar id is 703790.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.719 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP13A2	NM_022089.4	c.705+228A>G		intron_variant		ENST00000326735.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP13A2	ENST00000326735.13	c.705+228A>G		intron_variant		1	NM_022089.4	A1
	ENST00000446261.1	n.188-2837T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.561 AC: 85241 AN: 151966 Hom.: 24879 Cov.: 33

Gnomad AFR AF: 0.725

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.535

Gnomad ASJ AF: 0.513

Gnomad EAS AF: 0.714

Gnomad SAS AF: 0.586

Gnomad FIN AF: 0.524

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.463

Gnomad OTH AF: 0.538

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

GnomAD4 genome AF: 0.561 AC: 85357 AN: 152086 Hom.: 24940 Cov.: 33 AF XY: 0.567 AC XY: 42187 AN XY: 74354

Gnomad4 AFR AF: 0.726

Gnomad4 AMR AF: 0.535

Gnomad4 ASJ AF: 0.513

Gnomad4 EAS AF: 0.715

Gnomad4 SAS AF: 0.586

Gnomad4 FIN AF: 0.524

Gnomad4 NFE AF: 0.463

Gnomad4 OTH AF: 0.544

Alfa AF: 0.526 Hom.: 3540

Bravo AF: 0.567

Asia WGS AF: 0.669 AC: 2325 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Kufor-Rakeb syndrome;C5567893:Autosomal recessive spastic paraplegia type 78 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 07, 2020

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 05, 2018

This variant is associated with the following publications: (PMID: 22285144) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.2
DANN	Benign	0.42

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: rs2871776; hg19: chr1-17328301; COSMIC: COSV58699256; COSMIC: COSV58699256;