7-103316937-T-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_014377.3(DNAJC2):c.1320A>G(p.Thr440=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00919 in 1,614,034 control chromosomes in the GnomAD database, including 121 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0071 (10 hom., cov: 32)
  • Exomes 𝑓: 0.0094 (111 hom.)
• Consequence: DNAJC2 NM_014377.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0160

Genes affected

DNAJC2 (HGNC:13192): (DnaJ heat shock protein family (Hsp40) member C2) This gene is a member of the M-phase phosphoprotein (MPP) family. The gene encodes a phosphoprotein with a J domain and a Myb DNA-binding domain which localizes to both the nucleus and the cytosol. The protein is capable of forming a heterodimeric complex that associates with ribosomes, acting as a molecular chaperone for nascent polypeptide chains as they exit the ribosome. This protein was identified as a leukemia-associated antigen and expression of the gene is upregulated in leukemic blasts. Also, chromosomal aberrations involving this gene are associated with primary head and neck squamous cell tumors. This gene has a pseudogene on chromosome 6. Alternatively spliced variants which encode different protein isoforms have been described. [provided by RefSeq, Jul 2008]

PMPCB (HGNC:9119): (peptidase, mitochondrial processing subunit beta) This gene is a member of the peptidase M16 family and encodes a protein with a zinc-binding motif. This protein is located in the mitochondrial matrix and catalyzes the cleavage of the leader peptides of precursor proteins newly imported into the mitochondria, though it only functions as part of a heterodimeric complex. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 7-103316937-T-C is Benign according to our data. Variant chr7-103316937-T-C is described in ClinVar as [Benign]. Clinvar id is 2673124.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.016 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 10 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAJC2	NM_014377.3	c.1320A>G	p.Thr440=	synonymous_variant	13/17	ENST00000379263.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAJC2	ENST00000379263.8	c.1320A>G	p.Thr440=	synonymous_variant	13/17	1	NM_014377.3	P1

Frequencies

GnomAD3 genomes AF: 0.00713 AC: 1085 AN: 152220 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.00188

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.00216

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.0240

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0102

Gnomad OTH AF: 0.00430

GnomAD3 exomes AF: 0.00809 AC: 2017 AN: 249456 Hom.: 32 AF XY: 0.00803 AC XY: 1087 AN XY: 135354

Gnomad AFR exome AF: 0.00129

Gnomad AMR exome AF: 0.00107

Gnomad ASJ exome AF: 0.00149

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000850

Gnomad FIN exome AF: 0.0282

Gnomad NFE exome AF: 0.0110

Gnomad OTH exome AF: 0.0101

GnomAD4 exome AF: 0.00940 AC: 13746 AN: 1461696 Hom.: 111 Cov.: 31 AF XY: 0.00912 AC XY: 6630 AN XY: 727180

Gnomad4 AFR exome AF: 0.00152

Gnomad4 AMR exome AF: 0.00134

Gnomad4 ASJ exome AF: 0.00138

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000939

Gnomad4 FIN exome AF: 0.0292

Gnomad4 NFE exome AF: 0.0104

Gnomad4 OTH exome AF: 0.00714

GnomAD4 genome AF: 0.00712 AC: 1085 AN: 152338 Hom.: 10 Cov.: 32 AF XY: 0.00701 AC XY: 522 AN XY: 74504

Gnomad4 AFR AF: 0.00188

Gnomad4 AMR AF: 0.00216

Gnomad4 ASJ AF: 0.00231

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000829

Gnomad4 FIN AF: 0.0240

Gnomad4 NFE AF: 0.0102

Gnomad4 OTH AF: 0.00425

Alfa AF: 0.00862 Hom.: 5

Bravo AF: 0.00505

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00938

EpiControl AF: 0.00776

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2024

DNAJC2: BP4, BP7, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
Cadd	Benign	5.9
Dann	Benign	0.54
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs61762984; hg19: chr7-102957384;