rs7540807

Variant names:

• chr1-65405314-T-G
• rs7540807
• NM_001256864.2:c.2228-556T>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.2228-556T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 152,236 control chromosomes in the GnomAD database, including 1,281 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 0.13 (1281 hom., cov: 33)
• Consequence: DNAJC6 NM_001256864.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.158
• Publications: 1 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAJC6	NM_001256864.2	c.2228-556T>G		intron_variant	Intron 15 of 18	ENST00000371069.5	NP_001243793.1
DNAJC6	NM_014787.4	c.2057-556T>G		intron_variant	Intron 15 of 18		NP_055602.1
DNAJC6	NM_001256865.2	c.2018-556T>G		intron_variant	Intron 16 of 19		NP_001243794.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAJC6	ENST00000371069.5	c.2228-556T>G		intron_variant	Intron 15 of 18	1	NM_001256864.2	ENSP00000360108.4
DNAJC6	ENST00000395325.7	c.2057-556T>G		intron_variant	Intron 15 of 18	1		ENSP00000378735.3
DNAJC6	ENST00000263441.11	c.2018-556T>G		intron_variant	Intron 16 of 19	2		ENSP00000263441.7

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19180 AN: 152118 Hom.: 1282 Cov.: 33

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.0726

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.0979

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0943

Gnomad OTH AF: 0.140

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

GnomAD4 genome AF: 0.126 AC: 19187 AN: 152236 Hom.: 1281 Cov.: 33 AF XY: 0.127 AC XY: 9455 AN XY: 74446

African (AFR) AF: 0.191 AC: 7949 AN: 41524

American (AMR) AF: 0.130 AC: 1990 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 475 AN: 3470

East Asian (EAS) AF: 0.0718 AC: 372 AN: 5180

South Asian (SAS) AF: 0.113 AC: 543 AN: 4818

European-Finnish (FIN) AF: 0.0979 AC: 1039 AN: 10608

Middle Eastern (MID) AF: 0.134 AC: 39 AN: 292

European-Non Finnish (NFE) AF: 0.0943 AC: 6416 AN: 68024

Other (OTH) AF: 0.140 AC: 295 AN: 2110

Alfa AF: 0.108 Hom.: 593

Bravo AF: 0.133

Asia WGS AF: 0.106 AC: 370 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.9
DANN	Benign	0.63
PhyloP100		-0.16
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: rs7540807; hg19: chr1-65870997;