2-219281929-G-A

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.230-10G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 1,613,740 control chromosomes in the GnomAD database, including 22,708 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2231 hom., cov: 32)

Exomes 𝑓: 0.16 ( 20477 hom. )

Consequence

DNAJB2
NM_006736.6 intron

Scores

Splicing: ADA: 0.0008840

Clinical Significance

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

Conservation

PhyloP100: 0.458

Publications

8 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=-0.78).

BP6

Variant 2-219281929-G-A is Benign according to our data. Variant chr2-219281929-G-A is described in ClinVar as Benign. ClinVar VariationId is 137119.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAJB2	NM_006736.6 link	c.230-10G>A		intron_variant	Intron 4 of 8	ENST00000336576.10	NP_006727.2	P25686-3
DNAJB2	NM_001039550.2 link	c.230-10G>A		intron_variant	Intron 4 of 9		NP_001034639.1	P25686-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAJB2	ENST00000336576.10 link	c.230-10G>A		intron_variant	Intron 4 of 8	1	NM_006736.6	ENSP00000338019.5		P25686-3

Frequencies

GnomAD3 genomes

AF:

0.161

AC:

24519

AN:

152090

Hom.:

2226

Cov.:

show subpopulations

Gnomad AFR

AF:

0.194

Gnomad AMI

AF:

0.161

Gnomad AMR

AF:

0.165

Gnomad ASJ

AF:

0.195

Gnomad EAS

AF:

0.0498

Gnomad SAS

AF:

0.206

Gnomad FIN

AF:

0.0573

Gnomad MID

AF:

0.275

Gnomad NFE

AF:

0.159

Gnomad OTH

AF:

0.199

GnomAD2 exomes

AF:

0.148

AC:

37101

AN:

250998

AF XY:

0.151

show subpopulations

Gnomad AFR exome

AF:

0.192

Gnomad AMR exome

AF:

0.135

Gnomad ASJ exome

AF:

0.207

Gnomad EAS exome

AF:

0.0544

Gnomad FIN exome

AF:

0.0628

Gnomad NFE exome

AF:

0.157

Gnomad OTH exome

AF:

0.169

GnomAD4 exome

AF:

0.162

AC:

236702

AN:

1461532

Hom.:

20477

Cov.:

AF XY:

0.163

AC XY:

118594

AN XY:

727046

show subpopulations

African (AFR)

AF:

0.200

AC:

6706

AN:

33466

American (AMR)

AF:

0.139

AC:

6220

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.204

AC:

5332

AN:

26108

East Asian (EAS)

AF:

0.0467

AC:

1855

AN:

39698

South Asian (SAS)

AF:

0.200

AC:

17273

AN:

86236

European-Finnish (FIN)

AF:

0.0665

AC:

3547

AN:

53356

Middle Eastern (MID)

AF:

0.265

AC:

1517

AN:

5726

European-Non Finnish (NFE)

AF:

0.165

AC:

183547

AN:

1111854

Other (OTH)

AF:

0.177

AC:

10705

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

11914

23827

35741

47654

59568

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6698

13396

20094

26792

33490

<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:

0.161

AC:

24525

AN:

152208

Hom.:

2231

Cov.:

AF XY:

0.158

AC XY:

11793

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.194

AC:

8049

AN:

41516

American (AMR)

AF:

0.164

AC:

2515

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.195

AC:

677

AN:

3470

East Asian (EAS)

AF:

0.0493

AC:

255

AN:

5172

South Asian (SAS)

AF:

0.207

AC:

1000

AN:

4826

European-Finnish (FIN)

AF:

0.0573

AC:

608

AN:

10614

Middle Eastern (MID)

AF:

0.279

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.159

AC:

10779

AN:

68002

Other (OTH)

AF:

0.196

AC:

413

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1021

2041

3062

4082

5103

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

270

540

810

1080

1350

<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:

0.160

Hom.:

2799

Bravo

AF:

0.171

Asia WGS

AF:

0.109

AC:

381

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

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

-0.78

CADD

Benign

7.4

(source)

DANN

Benign

0.71

PhyloP100

0.46

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00088

dbscSNV1_RF

Benign

0.042

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