chr1-16986788-C-T

Variant names:

• chr1-16986788-C-T
• rs56146840
• NM_022089.4:c.3235+17G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_022089.4(ATP13A2):​c.3235+17G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0252 in 1,609,774 control chromosomes in the GnomAD database, including 598 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.024 (48 hom., cov: 33)
  • Exomes 𝑓: 0.025 (550 hom.)
• Consequence: ATP13A2 NM_022089.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 1.45

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]

ENSG00000226526 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 1-16986788-C-T is Benign according to our data. Variant chr1-16986788-C-T is described in ClinVar as [Benign]. Clinvar id is 261542.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-16986788-C-T is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0239 (3637/152272) while in subpopulation NFE AF = 0.0263 (1789/68014). AF 95% confidence interval is 0.0253. There are 48 homozygotes in GnomAd4. There are 1781 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position FAILED quality control check.
• BS2: High Homozygotes in GnomAd4 at 48 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP13A2	NM_022089.4	c.3235+17G>A		intron_variant	Intron 27 of 28	ENST00000326735.13	NP_071372.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP13A2	ENST00000326735.13	c.3235+17G>A		intron_variant	Intron 27 of 28	1	NM_022089.4	ENSP00000327214.8

Frequencies

GnomAD3 genomes AF: 0.0239 AC: 3638 AN: 152154 Hom.: 48 Cov.: 33

Gnomad AFR AF: 0.0215

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.0258

Gnomad ASJ AF: 0.0236

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0141

Gnomad FIN AF: 0.0225

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0263

Gnomad OTH AF: 0.0296

GnomAD2 exomes AF: 0.0221 AC: 5304 AN: 240380 AF XY: 0.0225

Gnomad AFR exome AF: 0.0219

Gnomad AMR exome AF: 0.0224

Gnomad ASJ exome AF: 0.0285

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0235

Gnomad NFE exome AF: 0.0258

Gnomad OTH exome AF: 0.0309

GnomAD4 exome AF: 0.0253 AC: 36917 AN: 1457502 Hom.: 550 Cov.: 63 AF XY: 0.0251 AC XY: 18220 AN XY: 724960

Gnomad4 AFR exome AF: 0.0240 AC: 803 AN: 33420

Gnomad4 AMR exome AF: 0.0229 AC: 1015 AN: 44318

Gnomad4 ASJ exome AF: 0.0275 AC: 717 AN: 26048

Gnomad4 EAS exome AF: 0.0000253 AC: 1 AN: 39544

Gnomad4 SAS exome AF: 0.0175 AC: 1500 AN: 85836

Gnomad4 FIN exome AF: 0.0220 AC: 1147 AN: 52174

Gnomad4 NFE exome AF: 0.0269 AC: 29861 AN: 1110694

Gnomad4 Remaining exome AF: 0.0270 AC: 1624 AN: 60160

GnomAD4 genome AF: 0.0239 AC: 3637 AN: 152272 Hom.: 48 Cov.: 33 AF XY: 0.0239 AC XY: 1781 AN XY: 74442

Gnomad4 AFR AF: 0.0214 AC: 0.0213918 AN: 0.0213918

Gnomad4 AMR AF: 0.0258 AC: 0.0257516 AN: 0.0257516

Gnomad4 ASJ AF: 0.0236 AC: 0.0236175 AN: 0.0236175

Gnomad4 EAS AF: 0.000194 AC: 0.000193798 AN: 0.000193798

Gnomad4 SAS AF: 0.0141 AC: 0.0140728 AN: 0.0140728

Gnomad4 FIN AF: 0.0225 AC: 0.0225132 AN: 0.0225132

Gnomad4 NFE AF: 0.0263 AC: 0.0263034 AN: 0.0263034

Gnomad4 OTH AF: 0.0289 AC: 0.0288553 AN: 0.0288553

Alfa AF: 0.0262 Hom.: 14

Bravo AF: 0.0240

Asia WGS AF: 0.00577 AC: 20 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:4

May 01, 2017

Mayo Clinic Laboratories, Mayo Clinic

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.1
DANN	Benign	0.69
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs56146840; hg19: chr1-17313283; COSMIC: COSV58701097; COSMIC: COSV58701097;