Variant 2-219279847-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM2PP3_StrongPP5_Moderate

The NM_006736.6(DNAJB2):c.14A>G(p.Tyr5Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,461,726 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

DNAJB2
NM_006736.6 missense

Scores

Clinical Significance

Likely pathogenic criteria provided, single submitter P:2U:2

Conservation

PhyloP100: 8.40

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 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.973

PP5

Variant 2-219279847-A-G is Pathogenic according to our data. Variant chr2-219279847-A-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 183042.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAJB2	NM_006736.6 linkuse as main transcript	c.14A>G	p.Tyr5Cys	missense_variant	2/9	ENST00000336576.10	NP_006727.2
DNAJB2	NM_001039550.2 linkuse as main transcript	c.14A>G	p.Tyr5Cys	missense_variant	2/10		NP_001034639.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAJB2	ENST00000336576.10 linkuse as main transcript	c.14A>G	p.Tyr5Cys	missense_variant	2/9	1	NM_006736.6	ENSP00000338019		P25686-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000130

AC:

AN:

1461726

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

727180

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000171

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:2Uncertain:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Neuronopathy, distal hereditary motor, autosomal recessive 5

Pathogenic:2

Likely pathogenic, criteria provided, single submitter	research	Suna and Inan Kirac Foundation Neurodegeneration Research Laboratory, Koc University	Mar 31, 2020	- -
Pathogenic, no assertion criteria provided	literature only	OMIM	Nov 04, 2014	- -

Charcot-Marie-Tooth disease

Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

Inherited Neuropathy Consortium

- -

Autosomal recessive distal spinal muscular atrophy 2

Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

Inherited Neuropathy Consortium Ii, University Of Miami

Jan 06, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.98

BayesDel_addAF

Pathogenic

0.30

BayesDel_noAF

Pathogenic

0.19

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.53

D;T;.;T;T;.;T

Eigen

Uncertain

0.65

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.95

LIST_S2

Pathogenic

0.99

D;D;D;D;D;D;D

M_CAP

Pathogenic

0.56

MetaRNN

Pathogenic

0.97

D;D;D;D;D;D;D

MetaSVM

Uncertain

0.60

MutationAssessor

Pathogenic

4.2

H;.;H;.;.;.;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.83

PROVEAN

Pathogenic

-7.5

D;D;D;D;D;D;D

REVEL

Pathogenic

0.90

Sift

Pathogenic

0.0

D;D;D;D;D;D;D

Sift4G

Uncertain

0.016

D;D;D;D;D;D;D

Polyphen

0.92

P;.;P;.;.;.;.

Vest4

0.97

MutPred

0.85

Loss of phosphorylation at S5 (P = 0.0256);Loss of phosphorylation at S5 (P = 0.0256);Loss of phosphorylation at S5 (P = 0.0256);Loss of phosphorylation at S5 (P = 0.0256);Loss of phosphorylation at S5 (P = 0.0256);Loss of phosphorylation at S5 (P = 0.0256);Loss of phosphorylation at S5 (P = 0.0256);

MVP

0.96

MPC

0.92

ClinPred

1.0

GERP RS

2.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.93

gMVP

0.84

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over