rs2878

Positions:

• chr7-103313174-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004279.3(PMPCB):​c.*903A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 1,497,770 control chromosomes in the GnomAD database, including 21,030 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.23 (6360 hom., cov: 32)
  • Exomes 𝑓: 0.13 (14670 hom.)
• Consequence: PMPCB NM_004279.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.126

Genes affected

PMPCB (HGNC:9119): (peptidase, mitochondrial processing subunit beta) This gene is a member of the peptidase M16 family and encodes a protein with a zinc-binding motif. This protein is located in the mitochondrial matrix and catalyzes the cleavage of the leader peptides of precursor proteins newly imported into the mitochondria, though it only functions as part of a heterodimeric complex. [provided by RefSeq, Jul 2008]

DNAJC2 (HGNC:13192): (DnaJ heat shock protein family (Hsp40) member C2) This gene is a member of the M-phase phosphoprotein (MPP) family. The gene encodes a phosphoprotein with a J domain and a Myb DNA-binding domain which localizes to both the nucleus and the cytosol. The protein is capable of forming a heterodimeric complex that associates with ribosomes, acting as a molecular chaperone for nascent polypeptide chains as they exit the ribosome. This protein was identified as a leukemia-associated antigen and expression of the gene is upregulated in leukemic blasts. Also, chromosomal aberrations involving this gene are associated with primary head and neck squamous cell tumors. This gene has a pseudogene on chromosome 6. Alternatively spliced variants which encode different protein isoforms have been described. [provided by RefSeq, Jul 2008]

DNAJC2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.504 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PMPCB	NM_004279.3	c.*903A>G		3_prime_UTR_variant	13/13	ENST00000249269.9	NP_004270.2
DNAJC2	NM_014377.3	c.1637-73T>C		intron_variant		ENST00000379263.8	NP_055192.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PMPCB	ENST00000249269.9	c.*903A>G		3_prime_UTR_variant	13/13	1	NM_004279.3	ENSP00000249269.4
DNAJC2	ENST00000379263.8	c.1637-73T>C		intron_variant		1	NM_014377.3	ENSP00000368565.3

Frequencies

GnomAD3 genomes AF: 0.230 AC: 34998 AN: 152034 Hom.: 6345 Cov.: 32

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.0806

Gnomad EAS AF: 0.0514

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.189

GnomAD4 exome AF: 0.132 AC: 178013 AN: 1345618 Hom.: 14670 Cov.: 32 AF XY: 0.131 AC XY: 86997 AN XY: 662750

Gnomad4 AFR exome AF: 0.536

Gnomad4 AMR exome AF: 0.196

Gnomad4 ASJ exome AF: 0.0746

Gnomad4 EAS exome AF: 0.0603

Gnomad4 SAS exome AF: 0.150

Gnomad4 FIN exome AF: 0.147

Gnomad4 NFE exome AF: 0.121

Gnomad4 OTH exome AF: 0.147

GnomAD4 genome AF: 0.230 AC: 35050 AN: 152152 Hom.: 6360 Cov.: 32 AF XY: 0.227 AC XY: 16903 AN XY: 74386

Gnomad4 AFR AF: 0.510

Gnomad4 AMR AF: 0.170

Gnomad4 ASJ AF: 0.0806

Gnomad4 EAS AF: 0.0506

Gnomad4 SAS AF: 0.137

Gnomad4 FIN AF: 0.146

Gnomad4 NFE AF: 0.119

Gnomad4 OTH AF: 0.188

Alfa AF: 0.187 Hom.: 699

Bravo AF: 0.246

Asia WGS AF: 0.133 AC: 461 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.61
DANN	Benign	0.65

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: rs2878; hg19: chr7-102953621;