2-219280564-C-T

Variant names:

• chr2-219280564-C-T
• rs2276638
• NM_006736.6:c.66-14C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.639
• Publications: 15 publications found

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: Orphanet, ClinGen
• neuronopathy, distal hereditary motor, autosomal recessive 5

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006736.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJB2	NM_006736.6	MANE Select	c.66-14C>T		intron	N/A	NP_006727.2
	DNAJB2	NM_001039550.2		c.66-14C>T		intron	N/A	NP_001034639.1	P25686-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJB2	ENST00000336576.10	TSL:1 MANE Select	c.66-14C>T		intron	N/A	ENSP00000338019.5	P25686-3
	DNAJB2	ENST00000933785.1		c.66-14C>T		intron	N/A	ENSP00000603844.1
	DNAJB2	ENST00000392086.8	TSL:2	c.66-14C>T		intron	N/A	ENSP00000375936.4	P25686-2

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38899 AN: 151934 Hom.: 6552 Cov.: 32

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

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.: 29 AF XY: 0.184 AC XY: 133300 AN XY: 724392

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

GnomAD4 genome AF: 0.256 AC: 38943 AN: 152052 Hom.: 6571 Cov.: 32 AF XY: 0.251 AC XY: 18674 AN XY: 74372

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: 85 AN: 294

European-Non Finnish (NFE) AF: 0.172 AC: 11685 AN: 67992

Other (OTH) AF: 0.267 AC: 564 AN: 2112

Alfa AF: 0.198 Hom.: 2333

Bravo AF: 0.277

Asia WGS AF: 0.176 AC: 613 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Neuronopathy, distal hereditary motor, autosomal recessive 5 (2)
-	-	1	Charcot-Marie-Tooth disease (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	11
DANN	Benign	0.87
PhyloP100		0.64
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2276638; hg19: chr2-220145286; COSMIC: COSV60676083; COSMIC: COSV60676083;