12-15982409-A-G

Position:

• chr12-15982409-A-G

Variant summary

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

The NM_015954.4(DERA):​c.610A>G​(p.Lys204Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: DERA NM_015954.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.58

Genes affected

DERA (HGNC:24269): (deoxyribose-phosphate aldolase) Enables deoxyribose-phosphate aldolase activity. Involved in deoxyribonucleoside catabolic process. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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/exons	MANE	Protein	UniProt
DERA	NM_015954.4	c.610A>G	p.Lys204Glu	missense_variant	6/9	ENST00000428559.7	NP_057038.2
DERA	XM_024449001.2	c.346A>G	p.Lys116Glu	missense_variant	6/9		XP_024304769.1
DERA	NM_001300779.2	c.508+19462A>G		intron_variant			NP_001287708.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DERA	ENST00000428559.7	c.610A>G	p.Lys204Glu	missense_variant	6/9	1	NM_015954.4	ENSP00000416583.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 03, 2024

The c.610A>G (p.K204E) alteration is located in exon 6 (coding exon 6) of the DERA gene. This alteration results from a A to G substitution at nucleotide position 610, causing the lysine (K) at amino acid position 204 to be replaced by a glutamic acid (E). 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	Uncertain	0.43
BayesDel_addAF	Pathogenic	0.39	D
BayesDel_noAF	Pathogenic	0.32
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.36	T;T;.;.
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Pathogenic	0.98	D;D;D;D
M_CAP	Benign	0.029	D
MetaRNN	Uncertain	0.69	D;D;D;D
MetaSVM	Uncertain	-0.25	T
MutationAssessor	Uncertain	2.3	M;.;.;.
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-2.9	D;D;D;D
REVEL	Uncertain	0.39
Sift	Uncertain	0.0040	D;D;D;D
Sift4G	Uncertain	0.0060	D;D;D;D
Polyphen		0.75	P;.;.;.
Vest4		0.78
MutPred		0.58		Loss of ubiquitination at K204 (P = 0.0155);.;.;.;
MVP		0.62
MPC		0.22
ClinPred		0.99	D
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.92
gMVP		0.90

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-16135343;