Variant 10-80362573-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_032372.6(DYDC2):c.130G>A(p.Ala44Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,458,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

DYDC2
NM_032372.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.07

Variant links:

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 links:

DYDC2 (HGNC:):

DYDC2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05678919).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DYDC2	NM_032372.6 linkuse as main transcript	c.130G>A	p.Ala44Thr	missense_variant	3/5	ENST00000256039.3	NP_115748.1	Q96IM9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DYDC2	ENST00000256039.3 linkuse as main transcript	c.130G>A	p.Ala44Thr	missense_variant	3/5	2	NM_032372.6	ENSP00000256039.2		Q96IM9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250650

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135464

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1458840

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725102

show subpopulations

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:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.000111

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 09, 2024

The c.130G>A (p.A44T) alteration is located in exon 3 (coding exon 1) of the DYDC2 gene. This alteration results from a G to A substitution at nucleotide position 130, causing the alanine (A) at amino acid position 44 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

0.075

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.058

DANN

Benign

0.74

DEOGEN2

Benign

0.0046

T;T;T;T;T;T;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0065

LIST_S2

Benign

0.53

.;T;.;T;.;T;.

M_CAP

Benign

0.0029

MetaRNN

Benign

0.057

T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

L;.;L;L;L;.;L

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.60

N;N;N;N;.;N;N

REVEL

Benign

0.029

Sift

Benign

0.50

T;T;T;T;.;T;T

Sift4G

Benign

0.35

T;T;T;T;T;T;T

Polyphen

0.0010

B;.;B;B;B;.;B

Vest4

0.054

MutPred

0.23

Gain of phosphorylation at A44 (P = 0.032);.;Gain of phosphorylation at A44 (P = 0.032);Gain of phosphorylation at A44 (P = 0.032);Gain of phosphorylation at A44 (P = 0.032);Gain of phosphorylation at A44 (P = 0.032);Gain of phosphorylation at A44 (P = 0.032);

MVP

0.048

MPC

0.10

ClinPred

0.034

GERP RS

-9.2

Varity_R

0.034

gMVP

0.094

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over