chr1-16997010-C-T

Position:

chr1-16997010-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_022089.4(ATP13A2):c.1195+10G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00538 in 1,610,702 control chromosomes in the GnomAD database, including 52 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0056 ( 7 hom., cov: 32)

Exomes 𝑓: 0.0054 ( 45 hom. )

Consequence

ATP13A2
NM_022089.4 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -0.576

Variant links:

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 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 1-16997010-C-T is Benign according to our data. Variant chr1-16997010-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 194113.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-16997010-C-T is described in Lovd as [Likely_benign]. Variant chr1-16997010-C-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00561 (855/152324) while in subpopulation NFE AF= 0.00607 (413/68038). AF 95% confidence interval is 0.00559. There are 7 homozygotes in gnomad4. There are 480 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP13A2	NM_022089.4 linkuse as main transcript	c.1195+10G>A		intron_variant		ENST00000326735.13	NP_071372.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP13A2	ENST00000326735.13 linkuse as main transcript	c.1195+10G>A		intron_variant		1	NM_022089.4	ENSP00000327214	A1	Q9NQ11-1
	ENST00000446261.1 linkuse as main transcript	n.188-7633C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00562

AC:

855

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000893

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00288

Gnomad ASJ

AF:

0.0179

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.0258

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00607

Gnomad OTH

AF:

0.00622

GnomAD3 exomes

AF:

0.00627

AC:

1540

AN:

245694

Hom.:

AF XY:

0.00595

AC XY:

794

AN XY:

133470

show subpopulations

Gnomad AFR exome

AF:

0.000440

Gnomad AMR exome

AF:

0.00263

Gnomad ASJ exome

AF:

0.0173

Gnomad EAS exome

AF:

0.00143

Gnomad SAS exome

AF:

0.00108

Gnomad FIN exome

AF:

0.0257

Gnomad NFE exome

AF:

0.00565

Gnomad OTH exome

AF:

0.00830

GnomAD4 exome

AF:

0.00535

AC:

7806

AN:

1458378

Hom.:

Cov.:

AF XY:

0.00539

AC XY:

3909

AN XY:

725460

show subpopulations

Gnomad4 AFR exome

AF:

0.000779

Gnomad4 AMR exome

AF:

0.00265

Gnomad4 ASJ exome

AF:

0.0190

Gnomad4 EAS exome

AF:

0.000707

Gnomad4 SAS exome

AF:

0.00128

Gnomad4 FIN exome

AF:

0.0233

Gnomad4 NFE exome

AF:

0.00483

Gnomad4 OTH exome

AF:

0.00640

GnomAD4 genome

AF:

0.00561

AC:

855

AN:

152324

Hom.:

Cov.:

AF XY:

0.00645

AC XY:

480

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.000890

Gnomad4 AMR

AF:

0.00288

Gnomad4 ASJ

AF:

0.0179

Gnomad4 EAS

AF:

0.00135

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.0258

Gnomad4 NFE

AF:

0.00607

Gnomad4 OTH

AF:

0.00616

Alfa

AF:

0.00640

Hom.:

Bravo

AF:

0.00360

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 05, 2018	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	May 23, 2017	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Nov 07, 2014	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Feb 11, 2020	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -

Kufor-Rakeb syndrome

Benign:2

Likely benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 28, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

2.5

DANN

Benign

0.48

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over