2-182775039-T-G

Variant names:

• chr2-182775039-T-G
• rs288285
• NM_018981.4:c.2266-277T>G

Variant summary

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

The NM_018981.4(DNAJC10):​c.2266-277T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 151,478 control chromosomes in the GnomAD database, including 31,790 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 0.64 (31790 hom., cov: 30)
• Consequence: DNAJC10 NM_018981.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.289
• Publications: 2 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.696 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.2266-277T>G		intron	N/A	NP_061854.1
	DNAJC10	NM_001271581.3		c.2128-277T>G		intron	N/A	NP_001258510.1
	DNAJC10	NR_073365.2		n.3450-277T>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJC10	ENST00000264065.12	TSL:1 MANE Select	c.2266-277T>G		intron	N/A	ENSP00000264065.6
	DNAJC10	ENST00000616986.5	TSL:1	c.2128-277T>G		intron	N/A	ENSP00000479930.1
	DNAJC10	ENST00000418559.6	TSL:1	n.*1331-277T>G		intron	N/A	ENSP00000389483.1

Frequencies

GnomAD3 genomes AF: 0.644 AC: 97527 AN: 151368 Hom.: 31771 Cov.: 30

Gnomad AFR AF: 0.704

Gnomad AMI AF: 0.568

Gnomad AMR AF: 0.566

Gnomad ASJ AF: 0.779

Gnomad EAS AF: 0.501

Gnomad SAS AF: 0.639

Gnomad FIN AF: 0.623

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.633

Gnomad OTH AF: 0.676

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

GnomAD4 genome AF: 0.644 AC: 97578 AN: 151478 Hom.: 31790 Cov.: 30 AF XY: 0.641 AC XY: 47414 AN XY: 73966

African (AFR) AF: 0.703 AC: 29066 AN: 41334

American (AMR) AF: 0.566 AC: 8628 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.779 AC: 2705 AN: 3472

East Asian (EAS) AF: 0.502 AC: 2571 AN: 5120

South Asian (SAS) AF: 0.639 AC: 3063 AN: 4796

European-Finnish (FIN) AF: 0.623 AC: 6433 AN: 10324

Middle Eastern (MID) AF: 0.731 AC: 212 AN: 290

European-Non Finnish (NFE) AF: 0.633 AC: 42965 AN: 67876

Other (OTH) AF: 0.673 AC: 1418 AN: 2108

Alfa AF: 0.639 Hom.: 4023

Bravo AF: 0.637

Asia WGS AF: 0.585 AC: 2042 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.58
DANN	Benign	0.29
PhyloP100		-0.29
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: rs288285; hg19: chr2-183639766;