10-80366803-T-C

Position:

• chr10-80366803-T-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.386T>C​(p.Ile129Thr) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DYDC2 NM_032372.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.141

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=0.07956019).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DYDC2	NM_032372.6	c.386T>C	p.Ile129Thr	missense_variant	5/5	ENST00000256039.3	NP_115748.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DYDC2	ENST00000256039.3	c.386T>C	p.Ile129Thr	missense_variant	5/5	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

Nov 08, 2022

The c.386T>C (p.I129T) alteration is located in exon 5 (coding exon 3) of the DYDC2 gene. This alteration results from a T to C substitution at nucleotide position 386, causing the isoleucine (I) at amino acid position 129 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	0.13
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	1.7
DANN	Benign	0.61
DEOGEN2	Benign	0.0031	T;T;T;T;T;T
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.55	.;T;.;T;.;.
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.080	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L;.;L;L;L;L
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.1	N;N;N;N;.;N
REVEL	Benign	0.0050
Sift	Benign	0.30	T;T;T;T;.;T
Sift4G	Benign	0.18	T;T;T;T;T;T
Polyphen		0.010	B;.;B;B;B;B
Vest4		0.051
MutPred		0.23		Loss of stability (P = 0.0105);.;Loss of stability (P = 0.0105);Loss of stability (P = 0.0105);Loss of stability (P = 0.0105);Loss of stability (P = 0.0105);
MVP		0.16
MPC		0.14
ClinPred		0.065	T
GERP RS		1.9
Varity_R		0.041
gMVP		0.049

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: chr10-82126559;