2-24971864-G-T

Variant names:

• chr2-24971864-G-T
• NM_016544.3:c.41C>A

Variant summary

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

The NM_016544.3(DNAJC27):​c.41C>A​(p.Ser14Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,178 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S14C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: DNAJC27 NM_016544.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.52

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-AS1 (HGNC:42943): (DNAJC27 antisense RNA 1)

ACMG classification

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 rank	MANE	Protein	UniProt
DNAJC27	NM_016544.3	c.41C>A	p.Ser14Tyr	missense_variant	Exon 1 of 7	ENST00000264711.7	NP_057628.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAJC27	ENST00000264711.7	c.41C>A	p.Ser14Tyr	missense_variant	Exon 1 of 7	1	NM_016544.3	ENSP00000264711.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457178 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 724880

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: 0.0000190

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Pathogenic	29
DANN	Uncertain	0.98
DEOGEN2	Benign	0.039	T;.
Eigen	Benign	0.17
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.69	T;T
M_CAP	Benign	0.052	D
MetaRNN	Benign	0.33	T;T
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	1.2	L;L
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.2	N;.
REVEL	Benign	0.21
Sift	Uncertain	0.015	D;.
Sift4G	Uncertain	0.031	D;D
Polyphen		0.0040	B;B
Vest4		0.43
MutPred		0.52		Loss of disorder (P = 0.0043);Loss of disorder (P = 0.0043);
MVP		0.74
MPC		0.29
ClinPred		0.96	D
GERP RS		6.0
Varity_R		0.26
gMVP		0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.36		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.36		Position offset: 3

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-25194733; COSMIC: COSV99266638; COSMIC: COSV99266638;