rs288254

Positions:

• chr2-182743900-G-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAJC10	NM_018981.4	c.1306+188G>A		intron_variant		ENST00000264065.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAJC10	ENST00000264065.12	c.1306+188G>A		intron_variant		1	NM_018981.4	P1

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

Gnomad4 AFR AF: 0.800

Gnomad4 AMR AF: 0.576

Gnomad4 ASJ AF: 0.780

Gnomad4 EAS AF: 0.503

Gnomad4 SAS AF: 0.653

Gnomad4 FIN AF: 0.624

Gnomad4 NFE AF: 0.634

Gnomad4 OTH AF: 0.695

Alfa AF: 0.644 Hom.: 32995

Bravo AF: 0.670

Asia WGS AF: 0.598 AC: 2084 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.12
DANN	Benign	0.50

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

Publications

LitVar

Other links and lift over

dbSNP: rs288254; hg19: chr2-183608627;