rs2427549

Variant names:

• chr20-63916056-C-T
• rs2427549
• NM_025219.3:c.-11-12279C>T

Variant summary

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

The NM_025219.3(DNAJC5):​c.-11-12279C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 152,020 control chromosomes in the GnomAD database, including 10,738 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 0.34 (10738 hom., cov: 32)
• Consequence: DNAJC5 NM_025219.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.892
• Publications: 1 publications found

Genes affected

DNAJC5 (HGNC:16235): (DnaJ heat shock protein family (Hsp40) member C5) This gene is a member of the J protein family. J proteins function in many cellular processes by regulating the ATPase activity of 70 kDa heat shock proteins. The encoded protein plays a role in membrane trafficking and protein folding, and has been shown to have anti-neurodegenerative properties. The encoded protein is known to play a role in cystic fibrosis and Huntington's disease. A pseudogene of this gene is located on the short arm of chromosome 8. [provided by RefSeq, Nov 2010]

DNAJC5 Gene-Disease associations (from GenCC):

• ceroid lipofuscinosis, neuronal, 4 (Kufs type)

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• adult neuronal ceroid lipofuscinosis

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen

ENSG00000290226 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.79 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025219.3. 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
	DNAJC5	NM_025219.3	MANE Select	c.-11-12279C>T		intron	N/A	NP_079495.1	Q9H3Z4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJC5	ENST00000360864.9	TSL:1 MANE Select	c.-11-12279C>T		intron	N/A	ENSP00000354111.4	Q9H3Z4-1
	DNAJC5	ENST00000898575.1		c.-6-12284C>T		intron	N/A	ENSP00000568634.1
	DNAJC5	ENST00000898576.1		c.-11-12279C>T		intron	N/A	ENSP00000568635.1

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52203 AN: 151902 Hom.: 10701 Cov.: 32

Gnomad AFR AF: 0.488

Gnomad AMI AF: 0.284

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.811

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.331

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.221

Gnomad OTH AF: 0.319

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

GnomAD4 genome AF: 0.344 AC: 52295 AN: 152020 Hom.: 10738 Cov.: 32 AF XY: 0.352 AC XY: 26175 AN XY: 74308

African (AFR) AF: 0.489 AC: 20260 AN: 41450

American (AMR) AF: 0.410 AC: 6266 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 747 AN: 3472

East Asian (EAS) AF: 0.810 AC: 4188 AN: 5168

South Asian (SAS) AF: 0.274 AC: 1321 AN: 4820

European-Finnish (FIN) AF: 0.331 AC: 3498 AN: 10558

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.221 AC: 15019 AN: 67972

Other (OTH) AF: 0.325 AC: 687 AN: 2112

Alfa AF: 0.300 Hom.: 1041

Bravo AF: 0.362

Asia WGS AF: 0.553 AC: 1920 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.4
DANN	Benign	0.50
PhyloP100		-0.89
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: rs2427549; hg19: chr20-62547409;