Variant chr2-24951455-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_016544.3(DNAJC27):c.628C>T(p.Arg210Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000151 in 1,613,882 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

DNAJC27
NM_016544.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.28

Variant links:

Genes affected

DNAJC27 (HGNC:30290): (DnaJ heat shock protein family (Hsp40) member C27) Predicted to enable GTPase activity. Predicted to be involved in intracellular protein transport and positive regulation of MAPK cascade. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

DNAJC27 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAJC27	NM_016544.3 linkuse as main transcript	c.628C>T	p.Arg210Cys	missense_variant	6/7	ENST00000264711.7	NP_057628.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAJC27	ENST00000264711.7 linkuse as main transcript	c.628C>T	p.Arg210Cys	missense_variant	6/7	1	NM_016544.3	ENSP00000264711	P1	Q9NZQ0-1
DNAJC27	ENST00000534855.5 linkuse as main transcript	c.529-3707C>T		intron_variant		1		ENSP00000440086		Q9NZQ0-3
DNAJC27	ENST00000380809.7 linkuse as main transcript	c.*496C>T		3_prime_UTR_variant, NMD_transcript_variant	8/9	2		ENSP00000370187		Q9NZQ0-2

Frequencies

GnomAD3 genomes

AF:

0.000145

AC:

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000944

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000108

AC:

AN:

251146

Hom.:

AF XY:

0.0000737

AC XY:

AN XY:

135732

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000175

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.000141

Gnomad OTH exome

AF:

0.000490

GnomAD4 exome

AF:

0.000151

AC:

221

AN:

1461598

Hom.:

Cov.:

AF XY:

0.000139

AC XY:

101

AN XY:

727086

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000201

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.000173

Gnomad4 OTH exome

AF:

0.000166

GnomAD4 genome

AF:

0.000144

AC:

AN:

152284

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000944

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000134

Hom.:

Bravo

AF:

0.000155

ExAC

AF:

0.0000412

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000178

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 01, 2022

The c.628C>T (p.R210C) alteration is located in exon 6 (coding exon 6) of the DNAJC27 gene. This alteration results from a C to T substitution at nucleotide position 628, causing the arginine (R) at amino acid position 210 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.13

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.18

Eigen

Uncertain

0.57

Eigen_PC

Uncertain

0.62

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.97

M_CAP

Benign

0.018

MetaRNN

Uncertain

0.46

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-1.7

REVEL

Benign

0.28

Sift

Uncertain

0.0090

Sift4G

Uncertain

0.032

Polyphen

1.0

Vest4

0.76

MVP

0.49

MPC

0.77

ClinPred

0.27

GERP RS

5.4

Varity_R

0.25

gMVP

0.73

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