2-219281954-G-T

Position:

• chr2-219281954-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006736.6(DNAJB2):​c.245G>T​(p.Arg82Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,826 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: DNAJB2 NM_006736.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.60

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08566034).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAJB2	NM_006736.6	c.245G>T	p.Arg82Leu	missense_variant	5/9	ENST00000336576.10	NP_006727.2
DNAJB2	NM_001039550.2	c.245G>T	p.Arg82Leu	missense_variant	5/10		NP_001034639.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAJB2	ENST00000336576.10	c.245G>T	p.Arg82Leu	missense_variant	5/9	1	NM_006736.6	ENSP00000338019.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461826 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727210

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: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.015	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	19
DANN	Benign	0.83
DEOGEN2	Benign	0.17	T;T;.;T;T;.;T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.84	T;T;T;T;T;T;D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.086	T;T;T;T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.5	M;.;M;.;.;.;.
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-2.8	D;D;D;D;D;D;D
REVEL	Benign	0.11
Sift	Benign	0.29	T;T;T;T;T;T;T
Sift4G	Benign	0.60	T;T;T;T;T;T;T
Polyphen		0.011	B;.;B;.;.;.;.
Vest4		0.43
MutPred		0.34		Loss of methylation at R82 (P = 0.0091);Loss of methylation at R82 (P = 0.0091);Loss of methylation at R82 (P = 0.0091);Loss of methylation at R82 (P = 0.0091);Loss of methylation at R82 (P = 0.0091);Loss of methylation at R82 (P = 0.0091);Loss of methylation at R82 (P = 0.0091);
MVP		0.49
MPC		0.37
ClinPred		0.32	T
GERP RS		2.3
Varity_R		0.081
gMVP		0.67

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

Other links and lift over

dbSNP: rs576205050; hg19: chr2-220146676;