rs4920608

Variant names:

• chr1-16992792-C-T
• rs4920608
• NM_022089.4:c.1750-211G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_022089.4(ATP13A2):​c.1750-211G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.548 in 152,190 control chromosomes in the GnomAD database, including 23,538 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.55 (23538 hom., cov: 35)
• Consequence: ATP13A2 NM_022089.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.279
• Publications: 21 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 1-16992792-C-T is Benign according to our data. Variant chr1-16992792-C-T is described in ClinVar as Benign. ClinVar VariationId is 1238030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.63 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.1750-211G>A		intron	N/A	NP_071372.1
	ATP13A2	NM_001141973.3		c.1735-211G>A		intron	N/A	NP_001135445.1
	ATP13A2	NM_001141974.3		c.1735-211G>A		intron	N/A	NP_001135446.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP13A2	ENST00000326735.13	TSL:1 MANE Select	c.1750-211G>A		intron	N/A	ENSP00000327214.8
	ATP13A2	ENST00000452699.5	TSL:1	c.1735-211G>A		intron	N/A	ENSP00000413307.1
	ATP13A2	ENST00000341676.9	TSL:1	c.1735-211G>A		intron	N/A	ENSP00000341115.5

Frequencies

GnomAD3 genomes AF: 0.548 AC: 83295 AN: 152072 Hom.: 23530 Cov.: 35

Gnomad AFR AF: 0.441

Gnomad AMI AF: 0.637

Gnomad AMR AF: 0.540

Gnomad ASJ AF: 0.625

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.493

Gnomad FIN AF: 0.535

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.635

Gnomad OTH AF: 0.557

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

GnomAD4 genome AF: 0.548 AC: 83332 AN: 152190 Hom.: 23538 Cov.: 35 AF XY: 0.540 AC XY: 40144 AN XY: 74396

African (AFR) AF: 0.441 AC: 18325 AN: 41548

American (AMR) AF: 0.540 AC: 8254 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.625 AC: 2168 AN: 3470

East Asian (EAS) AF: 0.280 AC: 1451 AN: 5176

South Asian (SAS) AF: 0.494 AC: 2383 AN: 4828

European-Finnish (FIN) AF: 0.535 AC: 5655 AN: 10574

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.635 AC: 43192 AN: 67996

Other (OTH) AF: 0.549 AC: 1162 AN: 2116

Alfa AF: 0.601 Hom.: 35208

Bravo AF: 0.544

Asia WGS AF: 0.369 AC: 1285 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	3.5
DANN	Benign	0.84
PhyloP100		-0.28
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: rs4920608; hg19: chr1-17319287;