Variant chr11-104036929-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001001711.3(DDI1):c.107C>G(p.Ala36Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

DDI1
NM_001001711.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.90

Variant links:

Genes affected

DDI1 (HGNC:18961): (DNA damage inducible 1 homolog 1) Predicted to enable aspartic-type endopeptidase activity. Involved in several processes, including cellular response to hydroxyurea; proteasomal protein catabolic process; and regulation of DNA stability. [provided by Alliance of Genome Resources, Apr 2022]

DDI1 links:

PDGFD (HGNC:30620): (platelet derived growth factor D) The protein encoded by this gene is a member of the platelet-derived growth factor family. The four members of this family are mitogenic factors for cells of mesenchymal origin and are characterized by a core motif of eight cysteines, seven of which are found in this factor. This gene product only forms homodimers and, therefore, does not dimerize with the other three family members. It differs from alpha and beta members of this family in having an unusual N-terminal domain, the CUB domain. Two splice variants have been identified for this gene. [provided by RefSeq, Jul 2008]

PDGFD links:

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ACMG classification

Classification made for transcript

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=0.22870731).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
DDI1	NM_001001711.3 linkuse as main transcript	c.107C>G	p.Ala36Gly	missense_variant	1/1	ENST00000302259.5
PDGFD	NM_025208.5 linkuse as main transcript	c.125-36674G>C		intron_variant		ENST00000393158.7
PDGFD	NM_033135.4 linkuse as main transcript	c.125-36692G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDI1	ENST00000302259.5 linkuse as main transcript	c.107C>G	p.Ala36Gly	missense_variant	1/1		NM_001001711.3	P1
PDGFD	ENST00000393158.7 linkuse as main transcript	c.125-36674G>C		intron_variant		1	NM_025208.5	P1	Q9GZP0-1
PDGFD	ENST00000302251.9 linkuse as main transcript	c.125-36692G>C		intron_variant		1			Q9GZP0-2
PDGFD	ENST00000529268.1 linkuse as main transcript	c.98G>C	p.Arg33Pro	missense_variant	1/4	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461880

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727240

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

May 20, 2024

The c.107C>G (p.A36G) alteration is located in exon 1 (coding exon 1) of the DDI1 gene. This alteration results from a C to G substitution at nucleotide position 107, causing the alanine (A) at amino acid position 36 to be replaced by a glycine (G). 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

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.068

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.31

LIST_S2

Benign

0.85

M_CAP

Benign

0.0044

MetaRNN

Benign

0.23

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

-2.2

REVEL

Benign

0.10

Sift

Benign

0.049

Sift4G

Benign

0.34

Polyphen

0.075

Vest4

0.094

MutPred

0.51

Loss of ubiquitination at K31 (P = 0.0709);

MVP

0.85

MPC

0.38

ClinPred

0.081

GERP RS

-0.29

Varity_R

0.082

gMVP

0.27

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over