1-17001705-A-T

Variant names:

• chr1-17001705-A-T
• rs6657613
• NM_022089.4:c.705+329T>A

Variant summary

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

The NM_022089.4(ATP13A2):​c.705+329T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 152,022 control chromosomes in the GnomAD database, including 13,501 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 0.40 (13501 hom., cov: 31)
• Consequence: ATP13A2 NM_022089.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.303
• Publications: 16 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: Genomics England PanelApp, G2P, ClinGen, Labcorp Genetics (formerly Invitae), Illumina
• 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

ENSG00000226526 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.506 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.705+329T>A		intron	N/A	NP_071372.1	Q9NQ11-1
	ATP13A2	NM_001141973.3		c.690+329T>A		intron	N/A	NP_001135445.1	Q9NQ11-3
	ATP13A2	NM_001141974.3		c.690+329T>A		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.705+329T>A		intron	N/A	ENSP00000327214.8	Q9NQ11-1
	ATP13A2	ENST00000452699.5	TSL:1	c.690+329T>A		intron	N/A	ENSP00000413307.1	Q9NQ11-3
	ATP13A2	ENST00000341676.9	TSL:1	c.690+329T>A		intron	N/A	ENSP00000341115.5	Q9NQ11-2

Frequencies

GnomAD3 genomes AF: 0.400 AC: 60686 AN: 151904 Hom.: 13498 Cov.: 31

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.470

Gnomad AMR AF: 0.437

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.409

Gnomad FIN AF: 0.455

Gnomad MID AF: 0.420

Gnomad NFE AF: 0.510

Gnomad OTH AF: 0.416

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

GnomAD4 genome AF: 0.399 AC: 60690 AN: 152022 Hom.: 13501 Cov.: 31 AF XY: 0.395 AC XY: 29330 AN XY: 74308

African (AFR) AF: 0.195 AC: 8095 AN: 41494

American (AMR) AF: 0.437 AC: 6677 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.465 AC: 1614 AN: 3468

East Asian (EAS) AF: 0.281 AC: 1447 AN: 5154

South Asian (SAS) AF: 0.410 AC: 1977 AN: 4824

European-Finnish (FIN) AF: 0.455 AC: 4798 AN: 10554

Middle Eastern (MID) AF: 0.428 AC: 125 AN: 292

European-Non Finnish (NFE) AF: 0.510 AC: 34662 AN: 67954

Other (OTH) AF: 0.411 AC: 867 AN: 2110

Alfa AF: 0.451 Hom.: 2029

Bravo AF: 0.390

Asia WGS AF: 0.319 AC: 1111 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.59
DANN	Benign	0.75
PhyloP100		-0.30
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: rs6657613; hg19: chr1-17328200;