10-80352456-A-C

Position:

chr10-80352456-A-C

Variant summary

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

The NM_001269053.2(DYDC1):c.146T>G(p.Leu49Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00001 in 1,597,482 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

DYDC1
NM_001269053.2 missense, splice_region

Scores

Splicing: ADA: 0.0001733

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.210

Variant links:

Genes affected

DYDC1 (HGNC:23460): (DPY30 domain containing 1) This gene encodes a member of a family of proteins that contains a DPY30 domain. The encoded protein is involved in acrosome formation during spermatid development. 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]

DYDC1 links:

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:

Genome browser will be placed here

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=0.033526897).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DYDC1	NM_001269053.2 linkuse as main transcript	c.146T>G	p.Leu49Arg	missense_variant, splice_region_variant	2/7	ENST00000372202.6	NP_001255982.1	Q8WWB3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DYDC1	ENST00000372202.6 linkuse as main transcript	c.146T>G	p.Leu49Arg	missense_variant, splice_region_variant	2/7	3	NM_001269053.2	ENSP00000361276.1		Q8WWB3-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000126

AC:

AN:

238680

Hom.:

AF XY:

0.00

AC XY:

AN XY:

129026

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:

0.0000273

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000104

AC:

AN:

1445320

Hom.:

Cov.:

AF XY:

0.00000835

AC XY:

AN XY:

718250

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:

0.0000136

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152162

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.0000247

AC:

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

Oct 29, 2024

The c.146T>G (p.L49R) alteration is located in exon 3 (coding exon 1) of the DYDC1 gene. This alteration results from a T to G substitution at nucleotide position 146, causing the leucine (L) at amino acid position 49 to be replaced by an arginine (R). 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

0.080

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.34

CADD

Benign

7.9

DANN

Benign

0.78

DEOGEN2

Benign

0.021

T;T;T;T;T

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.038

LIST_S2

Benign

0.57

.;T;.;T;T

M_CAP

Benign

0.0040

MetaRNN

Benign

0.034

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

M;M;M;.;.

PrimateAI

Benign

0.37

PROVEAN

Benign

1.6

N;N;N;N;N

REVEL

Benign

0.17

Sift

Benign

0.82

T;T;T;T;T

Sift4G

Benign

0.49

T;T;T;.;T

Polyphen

0.22

B;B;B;.;.

Vest4

0.39

MutPred

0.20

Gain of MoRF binding (P = 0.0145);Gain of MoRF binding (P = 0.0145);Gain of MoRF binding (P = 0.0145);Gain of MoRF binding (P = 0.0145);Gain of MoRF binding (P = 0.0145);

MVP

0.11

MPC

0.18

ClinPred

0.097

GERP RS

-1.4

Varity_R

0.12

gMVP

0.14

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00017

dbscSNV1_RF

Benign

0.018

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

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