7-103316937-T-C

Variant names:

• chr7-103316937-T-C
• rs61762984
• NM_014377.3:c.1320A>G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_014377.3(DNAJC2):​c.1320A>G​(p.Thr440Thr) 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
• Publications: 5 publications found

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]

PMPCB Gene-Disease associations (from GenCC):

• multiple mitochondrial dysfunctions syndrome 6

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Illumina, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014377.3. 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
	DNAJC2	NM_014377.3	MANE Select	c.1320A>G	p.Thr440Thr	synonymous	Exon 13 of 17	NP_055192.1	Q99543-1
	DNAJC2	NM_001129887.3		c.1161A>G	p.Thr387Thr	synonymous	Exon 11 of 15	NP_001123359.1	Q99543-2
	DNAJC2	NM_001362667.2		c.1098A>G	p.Thr366Thr	synonymous	Exon 13 of 17	NP_001349596.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJC2	ENST00000379263.8	TSL:1 MANE Select	c.1320A>G	p.Thr440Thr	synonymous	Exon 13 of 17	ENSP00000368565.3	Q99543-1
	DNAJC2	ENST00000249270.11	TSL:1	c.1161A>G	p.Thr387Thr	synonymous	Exon 11 of 15	ENSP00000249270.7	Q99543-2
	DNAJC2	ENST00000464253.5	TSL:1	n.1263A>G		non_coding_transcript_exon	Exon 12 of 16

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

GnomAD2 exomes AF: 0.00809 AC: 2017 AN: 249456 AF XY: 0.00803

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 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

African (AFR) AF: 0.00152 AC: 51 AN: 33480

American (AMR) AF: 0.00134 AC: 60 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00138 AC: 36 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.000939 AC: 81 AN: 86256

European-Finnish (FIN) AF: 0.0292 AC: 1557 AN: 53338

Middle Eastern (MID) AF: 0.000693 AC: 4 AN: 5768

European-Non Finnish (NFE) AF: 0.0104 AC: 11526 AN: 1111910

Other (OTH) AF: 0.00714 AC: 431 AN: 60392

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

African (AFR) AF: 0.00188 AC: 78 AN: 41590

American (AMR) AF: 0.00216 AC: 33 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00231 AC: 8 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000829 AC: 4 AN: 4828

European-Finnish (FIN) AF: 0.0240 AC: 255 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0102 AC: 694 AN: 68020

Other (OTH) AF: 0.00425 AC: 9 AN: 2116

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

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	5.9
DANN	Benign	0.54
PhyloP100		-0.016
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=93/7	polymorphism

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: rs61762984; hg19: chr7-102957384;