rs2296481

Variant names:

• chr1-65379393-C-T
• rs2296481
• NM_001256864.2:c.544-9C>T

Variant summary

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

The NM_001256864.2(DNAJC6):​c.544-9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 1,612,582 control chromosomes in the GnomAD database, including 32,548 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (8482 hom., cov: 32)
  • Exomes 𝑓: 0.12 (24066 hom.)
• Consequence: DNAJC6 NM_001256864.2 intron
• Scores: Splicing: ADA: 0.001528
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.341
• Publications: 13 publications found

Genes affected

DNAJC6 (HGNC:15469): (DnaJ heat shock protein family (Hsp40) member C6) DNAJC6 belongs to the evolutionarily conserved DNAJ/HSP40 family of proteins, which regulate molecular chaperone activity by stimulating ATPase activity. DNAJ proteins may have up to 3 distinct domains: a conserved 70-amino acid J domain, usually at the N terminus, a glycine/phenylalanine (G/F)-rich region, and a cysteine-rich domain containing 4 motifs resembling a zinc finger domain (Ohtsuka and Hata, 2000 [PubMed 11147971]).[supplied by OMIM, Mar 2008]

DNAJC6 Gene-Disease associations (from GenCC):

• juvenile onset Parkinson disease 19A

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics
• atypical juvenile parkinsonism

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• young-onset Parkinson disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 1-65379393-C-T is Benign according to our data. Variant chr1-65379393-C-T is described in ClinVar as Benign. ClinVar VariationId is 1170298.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAJC6	NM_001256864.2	c.544-9C>T		intron_variant	Intron 4 of 18	ENST00000371069.5	NP_001243793.1
DNAJC6	NM_014787.4	c.373-9C>T		intron_variant	Intron 4 of 18		NP_055602.1
DNAJC6	NM_001256865.2	c.334-9C>T		intron_variant	Intron 5 of 19		NP_001243794.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAJC6	ENST00000371069.5	c.544-9C>T		intron_variant	Intron 4 of 18	1	NM_001256864.2	ENSP00000360108.4

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38236 AN: 151866 Hom.: 8461 Cov.: 32

Gnomad AFR AF: 0.560

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.611

Gnomad SAS AF: 0.305

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.143

Gnomad NFE AF: 0.0646

Gnomad OTH AF: 0.212

GnomAD2 exomes AF: 0.212 AC: 53031 AN: 250576 AF XY: 0.202

Gnomad AFR exome AF: 0.568

Gnomad AMR exome AF: 0.288

Gnomad ASJ exome AF: 0.166

Gnomad EAS exome AF: 0.615

Gnomad FIN exome AF: 0.149

Gnomad NFE exome AF: 0.0658

Gnomad OTH exome AF: 0.157

GnomAD4 exome AF: 0.118 AC: 171806 AN: 1460598 Hom.: 24066 Cov.: 31 AF XY: 0.121 AC XY: 88212 AN XY: 726606

African (AFR) AF: 0.574 AC: 19175 AN: 33394

American (AMR) AF: 0.272 AC: 12136 AN: 44572

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 4284 AN: 26078

East Asian (EAS) AF: 0.637 AC: 25267 AN: 39682

South Asian (SAS) AF: 0.304 AC: 26140 AN: 86068

European-Finnish (FIN) AF: 0.146 AC: 7807 AN: 53398

Middle Eastern (MID) AF: 0.175 AC: 1009 AN: 5766

European-Non Finnish (NFE) AF: 0.0597 AC: 66291 AN: 1111330

Other (OTH) AF: 0.161 AC: 9697 AN: 60310

GnomAD4 genome AF: 0.252 AC: 38314 AN: 151984 Hom.: 8482 Cov.: 32 AF XY: 0.259 AC XY: 19216 AN XY: 74294

African (AFR) AF: 0.560 AC: 23208 AN: 41414

American (AMR) AF: 0.216 AC: 3295 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.165 AC: 572 AN: 3468

East Asian (EAS) AF: 0.611 AC: 3140 AN: 5142

South Asian (SAS) AF: 0.304 AC: 1464 AN: 4820

European-Finnish (FIN) AF: 0.159 AC: 1679 AN: 10564

Middle Eastern (MID) AF: 0.140 AC: 41 AN: 292

European-Non Finnish (NFE) AF: 0.0646 AC: 4391 AN: 67990

Other (OTH) AF: 0.219 AC: 462 AN: 2112

Alfa AF: 0.151 Hom.: 1878

Bravo AF: 0.271

Asia WGS AF: 0.477 AC: 1660 AN: 3478

EpiCase AF: 0.0734

EpiControl AF: 0.0762

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

-

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

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

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided Benign:2

Aug 17, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Juvenile onset Parkinson disease 19A Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 11, 2023

Genome-Nilou Lab

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	-0.59
CADD	Benign	16
DANN	Benign	0.82
PhyloP100		0.34
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0015
dbscSNV1_RF	Benign	0.22
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: rs2296481; hg19: chr1-65845076;