chr7-103313101-C-T

Variant names:

• chr7-103313101-C-T
• rs372907875
• NM_014377.3:c.1637G>A

Variant summary

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

The NM_014377.3(DNAJC2):​c.1637G>A​(p.Gly546Asp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DNAJC2 NM_014377.3 missense, splice_region
• Scores: Splicing: ADA: 0.01182
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.68

Genes affected

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]

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]

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=0.19044581).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAJC2	NM_014377.3	c.1637G>A	p.Gly546Asp	missense_variant, splice_region_variant	Exon 16 of 17	ENST00000379263.8	NP_055192.1
PMPCB	NM_004279.3	c.*830C>T		3_prime_UTR_variant	Exon 13 of 13	ENST00000249269.9	NP_004270.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAJC2	ENST00000379263.8	c.1637G>A	p.Gly546Asp	missense_variant, splice_region_variant	Exon 16 of 17	1	NM_014377.3	ENSP00000368565.3
PMPCB	ENST00000249269.9	c.*830C>T		3_prime_UTR_variant	Exon 13 of 13	1	NM_004279.3	ENSP00000249269.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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	0.22
BayesDel_addAF	Uncertain	0.012	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.052	.;T
Eigen	Benign	-0.060
Eigen_PC	Benign	-0.053
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.81	T;T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.19	T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	2.0	.;M
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-1.5	N;N
REVEL	Uncertain	0.33
Sift	Benign	0.15	T;T
Sift4G	Benign	0.070	T;T
Polyphen		0.85	P;P
Vest4		0.33
MutPred		0.32		.;Gain of loop (P = 0.024);
MVP		0.47
MPC		0.32
ClinPred		0.60	D
GERP RS		3.6
Varity_R		0.11
gMVP		0.48

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.012
dbscSNV1_RF	Benign	0.26
SpliceAI score (max)		0.030		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: rs372907875; hg19: chr7-102953548;