rs56010635

Variant names:

• chr1-16991598-G-A
• rs56010635
• NM_022089.4:c.2251+136C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-16991598-G-A
• chr1-16991598-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_022089.4(ATP13A2):​c.2251+136C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000468 in 1,307,398 control chromosomes in the GnomAD database, including 3 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 0.0019 (3 hom., cov: 33)
  • Exomes 𝑓: 0.00028 (0 hom.)
• Consequence: ATP13A2 NM_022089.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.364
• Publications: 1 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

ENSG00000226526 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00186 (284/152290) while in subpopulation AFR AF = 0.00599 (249/41558). AF 95% confidence interval is 0.00538. There are 3 homozygotes in GnomAd4. There are 115 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP13A2	NM_022089.4	MANE Select	c.2251+136C>T		intron	N/A	NP_071372.1
	ATP13A2	NM_001141973.3		c.2236+136C>T		intron	N/A	NP_001135445.1
	ATP13A2	NM_001141974.3		c.2236+136C>T		intron	N/A	NP_001135446.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP13A2	ENST00000326735.13	TSL:1 MANE Select	c.2251+136C>T		intron	N/A	ENSP00000327214.8
	ATP13A2	ENST00000452699.5	TSL:1	c.2236+136C>T		intron	N/A	ENSP00000413307.1
	ATP13A2	ENST00000341676.9	TSL:1	c.2236+136C>T		intron	N/A	ENSP00000341115.5

Frequencies

GnomAD3 genomes AF: 0.00187 AC: 284 AN: 152172 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.00601

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00335

GnomAD4 exome AF: 0.000284 AC: 328 AN: 1155108 Hom.: 0 AF XY: 0.000257 AC XY: 150 AN XY: 583892

African (AFR) AF: 0.00640 AC: 174 AN: 27204

American (AMR) AF: 0.000890 AC: 38 AN: 42680

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23800

East Asian (EAS) AF: 0.0000529 AC: 2 AN: 37794

South Asian (SAS) AF: 0.0000254 AC: 2 AN: 78880

European-Finnish (FIN) AF: 0.0000226 AC: 1 AN: 44302

Middle Eastern (MID) AF: 0.00131 AC: 6 AN: 4574

European-Non Finnish (NFE) AF: 0.0000922 AC: 78 AN: 845852

Other (OTH) AF: 0.000540 AC: 27 AN: 50022

GnomAD4 genome AF: 0.00186 AC: 284 AN: 152290 Hom.: 3 Cov.: 33 AF XY: 0.00154 AC XY: 115 AN XY: 74478

African (AFR) AF: 0.00599 AC: 249 AN: 41558

American (AMR) AF: 0.00118 AC: 18 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68026

Other (OTH) AF: 0.00331 AC: 7 AN: 2114

Alfa AF: 0.00173 Hom.: 0

Bravo AF: 0.00207

Asia WGS AF: 0.00115 AC: 5 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.1
DANN	Benign	0.60
PhyloP100		-0.36

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: rs56010635; hg19: chr1-17318093;