11-104037001-C-T

Variant summary

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

The NM_001001711.3(DDI1):c.179C>T(p.Ser60Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DDI1 NM_001001711.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.73

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]

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDI1	NM_001001711.3	c.179C>T	p.Ser60Phe	missense_variant	1/1	ENST00000302259.5
PDGFD	NM_025208.5	c.125-36746G>A		intron_variant		ENST00000393158.7
PDGFD	NM_033135.4	c.125-36764G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDI1	ENST00000302259.5	c.179C>T	p.Ser60Phe	missense_variant	1/1		NM_001001711.3	P1
PDGFD	ENST00000393158.7	c.125-36746G>A		intron_variant		1	NM_025208.5	P1
PDGFD	ENST00000302251.9	c.125-36764G>A		intron_variant		1
PDGFD	ENST00000529268.1	c.26G>A	p.Gly9Glu	missense_variant	1/4	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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

Dec 20, 2021

The c.179C>T (p.S60F) alteration is located in exon 1 (coding exon 1) of the DDI1 gene. This alteration results from a C to T substitution at nucleotide position 179, causing the serine (S) at amino acid position 60 to be replaced by a phenylalanine (F). 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	0.29
BayesDel_addAF	Benign	-0.022	T
BayesDel_noAF	Benign	-0.18
Cadd	Uncertain	26
Dann	Uncertain	1.0
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.29	T
M_CAP	Uncertain	0.10	D
MetaRNN	Uncertain	0.60	D
MetaSVM	Uncertain	0.23	D
MutationTaster	Benign	1.0	D;D;D
PROVEAN	Benign	0.18	N
REVEL	Benign	0.18
Sift	Pathogenic	0.0	D
MutPred		0.60		Gain of catalytic residue at G9 (P = 0.0344);
MVP		0.61
ClinPred		1.0	D
GERP RS		5.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr11-103907729;