10-80362961-A-C

Position:

• chr10-80362961-A-C

Variant summary

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

The NM_032372.6(DYDC2):​c.158A>C​(p.Lys53Thr) variant causes a missense 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DYDC2 NM_032372.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.91

Genes affected

DYDC2 (HGNC:23468): (DPY30 domain containing 2) This gene encodes a member of a family of proteins that contains a DPY30 domain. This gene locus overlaps with a closely related gene on the opposite strand. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2012]

DYDC2 (HGNC:):

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=0.10747036).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DYDC2	NM_032372.6	c.158A>C	p.Lys53Thr	missense_variant	4/5	ENST00000256039.3	NP_115748.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DYDC2	ENST00000256039.3	c.158A>C	p.Lys53Thr	missense_variant	4/5	2	NM_032372.6	ENSP00000256039.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Sep 09, 2024

The c.158A>C (p.K53T) alteration is located in exon 4 (coding exon 2) of the DYDC2 gene. This alteration results from a A to C substitution at nucleotide position 158, causing the lysine (K) at amino acid position 53 to be replaced by a threonine (T). 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	0.11
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.021	T;T;T;T;T;T;T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.46	.;T;.;T;.;T;.
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.11	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N;.;N;N;N;.;N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-2.2	N;N;N;N;.;N;N
REVEL	Benign	0.060
Sift	Uncertain	0.011	D;D;D;D;.;D;D
Sift4G	Uncertain	0.013	D;D;D;D;D;D;D
Polyphen		0.0030	B;.;B;B;B;.;B
Vest4		0.17
MutPred		0.30		Loss of ubiquitination at K53 (P = 8e-04);.;Loss of ubiquitination at K53 (P = 8e-04);Loss of ubiquitination at K53 (P = 8e-04);Loss of ubiquitination at K53 (P = 8e-04);Loss of ubiquitination at K53 (P = 8e-04);Loss of ubiquitination at K53 (P = 8e-04);
MVP		0.36
MPC		0.14
ClinPred		0.46	T
GERP RS		3.8
Varity_R		0.15
gMVP		0.20

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr10-82122717;