2-219280564-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006736.6(DNAJB2):c.66-14C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 1,606,996 control chromosomes in the GnomAD database, including 34,076 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 6571 hom., cov: 32)

Exomes 𝑓: 0.18 ( 27505 hom. )

Consequence

DNAJB2
NM_006736.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.639

Publications

15 publications found

Variant links:

Genes affected

DNAJB2 (HGNC:5228): (DnaJ heat shock protein family (Hsp40) member B2) This gene is almost exclusively expressed in the brain, mainly in the neuronal layers. It encodes a protein that shows sequence similarity to bacterial DnaJ protein and the yeast homologs. In bacteria, this protein is implicated in protein folding and protein complex dissociation. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2011]

DNAJB2 Gene-Disease associations (from GenCC):

Charcot-Marie-Tooth disease axonal type 2T
Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
neuronopathy, distal hereditary motor, autosomal recessive 5
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

DNAJB2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 2-219280564-C-T is Benign according to our data. Variant chr2-219280564-C-T is described in ClinVar as Benign. ClinVar VariationId is 137118.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.476 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAJB2	NM_006736.6 link	c.66-14C>T		intron_variant	Intron 2 of 8	ENST00000336576.10	NP_006727.2
DNAJB2	NM_001039550.2 link	c.66-14C>T		intron_variant	Intron 2 of 9		NP_001034639.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAJB2	ENST00000336576.10 link	c.66-14C>T		intron_variant	Intron 2 of 8	1	NM_006736.6	ENSP00000338019.5

Frequencies

GnomAD3 genomes

AF:

0.256

AC:

38899

AN:

151934

Hom.:

6552

Cov.:

show subpopulations

Gnomad AFR

AF:

0.482

Gnomad AMI

AF:

0.169

Gnomad AMR

AF:

0.205

Gnomad ASJ

AF:

0.218

Gnomad EAS

AF:

0.151

Gnomad SAS

AF:

0.218

Gnomad FIN

AF:

0.0744

Gnomad MID

AF:

0.288

Gnomad NFE

AF:

0.172

Gnomad OTH

AF:

0.270

GnomAD2 exomes

AF:

0.188

AC:

46998

AN:

250174

AF XY:

0.186

show subpopulations

Gnomad AFR exome

AF:

0.490

Gnomad AMR exome

AF:

0.154

Gnomad ASJ exome

AF:

0.228

Gnomad EAS exome

AF:

0.152

Gnomad FIN exome

AF:

0.0812

Gnomad NFE exome

AF:

0.171

Gnomad OTH exome

AF:

0.199

GnomAD4 exome

AF:

0.184

AC:

267970

AN:

1454944

Hom.:

27505

Cov.:

AF XY:

0.184

AC XY:

133300

AN XY:

724392

show subpopulations

African (AFR)

AF:

0.493

AC:

16433

AN:

33322

American (AMR)

AF:

0.160

AC:

7155

AN:

44610

Ashkenazi Jewish (ASJ)

AF:

0.224

AC:

5835

AN:

26034

East Asian (EAS)

AF:

0.153

AC:

6076

AN:

39646

South Asian (SAS)

AF:

0.212

AC:

18285

AN:

86102

European-Finnish (FIN)

AF:

0.0832

AC:

4439

AN:

53328

Middle Eastern (MID)

AF:

0.287

AC:

1647

AN:

5732

European-Non Finnish (NFE)

AF:

0.177

AC:

195319

AN:

1106026

Other (OTH)

AF:

0.213

AC:

12781

AN:

60144

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

10570

21140

31709

42279

52849

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7178

14356

21534

28712

35890

<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:

0.256

AC:

38943

AN:

152052

Hom.:

6571

Cov.:

AF XY:

0.251

AC XY:

18674

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.482

AC:

19951

AN:

41396

American (AMR)

AF:

0.205

AC:

3125

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.218

AC:

755

AN:

3466

East Asian (EAS)

AF:

0.151

AC:

780

AN:

5172

South Asian (SAS)

AF:

0.219

AC:

1055

AN:

4820

European-Finnish (FIN)

AF:

0.0744

AC:

789

AN:

10610

Middle Eastern (MID)

AF:

0.289

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.172

AC:

11685

AN:

67992

Other (OTH)

AF:

0.267

AC:

564

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1320

2640

3959

5279

6599

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

376

752

1128

1504

1880

<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:

0.198

Hom.:

2333

Bravo

AF:

0.277

Asia WGS

AF:

0.176

AC:

613

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Neuronopathy, distal hereditary motor, autosomal recessive 5

Benign:2

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Charcot-Marie-Tooth disease

Benign:1

Molecular Genetics Laboratory, London Health Sciences Centre

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Apr 01, 2014

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Benign

0.87

PhyloP100

0.64

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over