rs288254

Variant names:

• chr2-182743900-G-A
• rs288254
• NM_018981.4:c.1306+188G>A

Variant summary

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

The NM_018981.4(DNAJC10):​c.1306+188G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.673 in 152,108 control chromosomes in the GnomAD database, including 35,151 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 0.67 (35151 hom., cov: 32)
• Consequence: DNAJC10 NM_018981.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.16
• Publications: 3 publications found

Genes affected

DNAJC10 (HGNC:24637): (DnaJ heat shock protein family (Hsp40) member C10) This gene encodes an endoplasmic reticulum co-chaperone which is part of the endoplasmic reticulum-associated degradation complex involved in recognizing and degrading misfolded proteins. The encoded protein reduces incorrect disulfide bonds in misfolded glycoproteins. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Oct 2012]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.793 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018981.4. 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
	DNAJC10	NM_018981.4	MANE Select	c.1306+188G>A		intron	N/A	NP_061854.1
	DNAJC10	NM_001271581.3		c.1168+188G>A		intron	N/A	NP_001258510.1
	DNAJC10	NR_073365.2		n.2490+188G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJC10	ENST00000264065.12	TSL:1 MANE Select	c.1306+188G>A		intron	N/A	ENSP00000264065.6
	DNAJC10	ENST00000616986.5	TSL:1	c.1168+188G>A		intron	N/A	ENSP00000479930.1
	DNAJC10	ENST00000418559.6	TSL:1	n.*296+188G>A		intron	N/A	ENSP00000389483.1

Frequencies

GnomAD3 genomes AF: 0.673 AC: 102263 AN: 151992 Hom.: 35116 Cov.: 32

Gnomad AFR AF: 0.800

Gnomad AMI AF: 0.569

Gnomad AMR AF: 0.576

Gnomad ASJ AF: 0.780

Gnomad EAS AF: 0.503

Gnomad SAS AF: 0.653

Gnomad FIN AF: 0.624

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.634

Gnomad OTH AF: 0.698

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

GnomAD4 genome AF: 0.673 AC: 102345 AN: 152108 Hom.: 35151 Cov.: 32 AF XY: 0.669 AC XY: 49719 AN XY: 74336

African (AFR) AF: 0.800 AC: 33215 AN: 41518

American (AMR) AF: 0.576 AC: 8796 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.780 AC: 2708 AN: 3472

East Asian (EAS) AF: 0.503 AC: 2607 AN: 5178

South Asian (SAS) AF: 0.653 AC: 3145 AN: 4818

European-Finnish (FIN) AF: 0.624 AC: 6587 AN: 10552

Middle Eastern (MID) AF: 0.741 AC: 218 AN: 294

European-Non Finnish (NFE) AF: 0.634 AC: 43080 AN: 67966

Other (OTH) AF: 0.695 AC: 1470 AN: 2116

Alfa AF: 0.647 Hom.: 43282

Bravo AF: 0.670

Asia WGS AF: 0.598 AC: 2084 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.12
DANN	Benign	0.50
PhyloP100		-2.2
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: rs288254; hg19: chr2-183608627;