1-65403893-A-G

Variant names:

• chr1-65403893-A-G
• rs2148683
• NM_001256864.2:c.2228-1977A>G

Variant summary

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

The NM_001256864.2(DNAJC6):​c.2228-1977A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 152,046 control chromosomes in the GnomAD database, including 15,087 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 0.44 (15087 hom., cov: 32)
• Consequence: DNAJC6 NM_001256864.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.319
• Publications: 4 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: Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.495 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJC6	NM_001256864.2	MANE Select	c.2228-1977A>G		intron	N/A	NP_001243793.1	O75061-2
	DNAJC6	NM_014787.4		c.2057-1977A>G		intron	N/A	NP_055602.1	O75061-1
	DNAJC6	NM_001256865.2		c.2018-1977A>G		intron	N/A	NP_001243794.1	O75061-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJC6	ENST00000371069.5	TSL:1 MANE Select	c.2228-1977A>G		intron	N/A	ENSP00000360108.4	O75061-2
	DNAJC6	ENST00000395325.7	TSL:1	c.2057-1977A>G		intron	N/A	ENSP00000378735.3	O75061-1
	DNAJC6	ENST00000263441.11	TSL:2	c.2018-1977A>G		intron	N/A	ENSP00000263441.7	O75061-4

Frequencies

GnomAD3 genomes AF: 0.444 AC: 67386 AN: 151928 Hom.: 15080 Cov.: 32

Gnomad AFR AF: 0.413

Gnomad AMI AF: 0.335

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.466

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.512

Gnomad FIN AF: 0.387

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.481

Gnomad OTH AF: 0.456

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

GnomAD4 genome AF: 0.443 AC: 67429 AN: 152046 Hom.: 15087 Cov.: 32 AF XY: 0.440 AC XY: 32716 AN XY: 74300

African (AFR) AF: 0.413 AC: 17126 AN: 41450

American (AMR) AF: 0.431 AC: 6587 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.466 AC: 1617 AN: 3470

East Asian (EAS) AF: 0.275 AC: 1423 AN: 5172

South Asian (SAS) AF: 0.512 AC: 2471 AN: 4824

European-Finnish (FIN) AF: 0.387 AC: 4092 AN: 10562

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.481 AC: 32673 AN: 67978

Other (OTH) AF: 0.453 AC: 956 AN: 2112

Alfa AF: 0.456 Hom.: 22169

Bravo AF: 0.438

Asia WGS AF: 0.371 AC: 1292 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.11
DANN	Benign	0.64
PhyloP100		-0.32
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: rs2148683; hg19: chr1-65869576;