Genetic Variant NM_014377.3:c.1320A>G (chr7-103316937-T-C) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0160

Publications

5 publications found

Variant links:

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]

DNAJC2 links:

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

PMPCB links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

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

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.:

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.00912

AC XY:

6630

AN XY:

727180

show subpopulations

African (AFR)

AF:

0.00152

AC:

AN:

33480

American (AMR)

AF:

0.00134

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00138

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.000939

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.0292

AC:

1557

AN:

53338

Middle Eastern (MID)

AF:

0.000693

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0104

AC:

11526

AN:

1111910

Other (OTH)

AF:

0.00714

AC:

431

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

675

1349

2024

2698

3373

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

438

876

1314

1752

2190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00712

AC:

1085

AN:

152338

Hom.:

Cov.:

AF XY:

0.00701

AC XY:

522

AN XY:

74504

show subpopulations

African (AFR)

AF:

0.00188

AC:

AN:

41590

American (AMR)

AF:

0.00216

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00231

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.000829

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0240

AC:

255

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0102

AC:

694

AN:

68020

Other (OTH)

AF:

0.00425

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

112

167

223

279

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00862

Hom.:

Bravo

AF:

0.00505

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00938

EpiControl

AF:

0.00776

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

5.9

(source)

DANN

Benign

0.54

PhyloP100

-0.016

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=93/7

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over