11-104037001-C-T

Variant names:

• chr11-104037001-C-T
• NM_001001711.3:c.179C>T

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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]

PDGFD Gene-Disease associations (from GenCC):

• pulmonary arterial hypertension

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ENSG00000300441 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001001711.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDI1	NM_001001711.3	MANE Select	c.179C>T	p.Ser60Phe	missense	Exon 1 of 1	NP_001001711.1	Q8WTU0
	PDGFD	NM_025208.5	MANE Select	c.125-36746G>A		intron	N/A	NP_079484.1	Q9GZP0-1
	PDGFD	NM_033135.4		c.125-36764G>A		intron	N/A	NP_149126.1	Q9GZP0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDI1	ENST00000302259.5	TSL:6 MANE Select	c.179C>T	p.Ser60Phe	missense	Exon 1 of 1	ENSP00000302805.3	Q8WTU0
	PDGFD	ENST00000393158.7	TSL:1 MANE Select	c.125-36746G>A		intron	N/A	ENSP00000376865.2	Q9GZP0-1
	PDGFD	ENST00000302251.9	TSL:1	c.125-36764G>A		intron	N/A	ENSP00000302193.5	Q9GZP0-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		3.7
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
PromoterAI		0.015	Neutral
Varity_R		0.49
Mutation Taster		=50/50

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

Other links and lift over

hg19: chr11-103907729;