rs2375699

Variant names:

• chr1-65342598-G-A
• rs2375699
• NM_001256864.2:c.194-22037G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-65342598-G-A
• chr1-65342598-G-C
• chr1-65342598-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001256864.2(DNAJC6):​c.194-22037G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.512 in 151,954 control chromosomes in the GnomAD database, including 20,324 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 0.51 (20324 hom., cov: 32)
• Consequence: DNAJC6 NM_001256864.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.225
• Publications: 3 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.553 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001256864.2. 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
	DNAJC6	NM_001256864.2	MANE Select	c.194-22037G>A		intron	N/A	NP_001243793.1
	DNAJC6	NM_014787.4		c.23-22037G>A		intron	N/A	NP_055602.1
	DNAJC6	NM_001256865.2		c.-130-3013G>A		intron	N/A	NP_001243794.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJC6	ENST00000371069.5	TSL:1 MANE Select	c.194-22037G>A		intron	N/A	ENSP00000360108.4
	DNAJC6	ENST00000395325.7	TSL:1	c.23-22037G>A		intron	N/A	ENSP00000378735.3
	DNAJC6	ENST00000263441.11	TSL:2	c.-130-3013G>A		intron	N/A	ENSP00000263441.7

Frequencies

GnomAD3 genomes AF: 0.512 AC: 77811 AN: 151838 Hom.: 20320 Cov.: 32

Gnomad AFR AF: 0.560

Gnomad AMI AF: 0.545

Gnomad AMR AF: 0.439

Gnomad ASJ AF: 0.530

Gnomad EAS AF: 0.331

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.529

Gnomad NFE AF: 0.542

Gnomad OTH AF: 0.541

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

GnomAD4 genome AF: 0.512 AC: 77843 AN: 151954 Hom.: 20324 Cov.: 32 AF XY: 0.500 AC XY: 37099 AN XY: 74258

African (AFR) AF: 0.559 AC: 23159 AN: 41414

American (AMR) AF: 0.438 AC: 6698 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.530 AC: 1839 AN: 3472

East Asian (EAS) AF: 0.331 AC: 1714 AN: 5178

South Asian (SAS) AF: 0.400 AC: 1924 AN: 4812

European-Finnish (FIN) AF: 0.367 AC: 3885 AN: 10572

Middle Eastern (MID) AF: 0.531 AC: 155 AN: 292

European-Non Finnish (NFE) AF: 0.542 AC: 36838 AN: 67916

Other (OTH) AF: 0.537 AC: 1135 AN: 2112

Alfa AF: 0.536 Hom.: 93557

Bravo AF: 0.522

Asia WGS AF: 0.352 AC: 1227 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	0.50
DANN	Benign	0.64
PhyloP100		-0.23
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: rs2375699; hg19: chr1-65808281;