rs260808

Variant names:

• chr11-104038438-C-A
• rs260808
• NM_001001711.3:c.*425C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001001711.3(DDI1):​c.*425C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 179,048 control chromosomes in the GnomAD database, including 3,610 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.18 (3509 hom., cov: 32)
  • Exomes 𝑓: 0.081 (101 hom.)
• Consequence: DDI1 NM_001001711.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0370
• Publications: 7 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDI1	NM_001001711.3	c.*425C>A		3_prime_UTR_variant	Exon 1 of 1	ENST00000302259.5	NP_001001711.1
PDGFD	NM_025208.5	c.125-38183G>T		intron_variant	Intron 1 of 6	ENST00000393158.7	NP_079484.1
PDGFD	NM_033135.4	c.125-38201G>T		intron_variant	Intron 1 of 6		NP_149126.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDI1	ENST00000302259.5	c.*425C>A		3_prime_UTR_variant	Exon 1 of 1	6	NM_001001711.3	ENSP00000302805.3
PDGFD	ENST00000393158.7	c.125-38183G>T		intron_variant	Intron 1 of 6	1	NM_025208.5	ENSP00000376865.2
PDGFD	ENST00000302251.9	c.125-38201G>T		intron_variant	Intron 1 of 6	1		ENSP00000302193.5
ENSG00000300441	ENST00000771685.1	n.181+37194C>A		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27149 AN: 152004 Hom.: 3482 Cov.: 32

Gnomad AFR AF: 0.357

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.0987

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.0208

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.0572

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.169

GnomAD4 exome AF: 0.0811 AC: 2183 AN: 26926 Hom.: 101 Cov.: 0 AF XY: 0.0806 AC XY: 1074 AN XY: 13328

African (AFR) AF: 0.314 AC: 66 AN: 210

American (AMR) AF: 0.0863 AC: 202 AN: 2342

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 37 AN: 234

East Asian (EAS) AF: 0.00822 AC: 6 AN: 730

South Asian (SAS) AF: 0.110 AC: 146 AN: 1322

European-Finnish (FIN) AF: 0.0614 AC: 915 AN: 14912

Middle Eastern (MID) AF: 0.150 AC: 3 AN: 20

European-Non Finnish (NFE) AF: 0.115 AC: 752 AN: 6552

Other (OTH) AF: 0.0927 AC: 56 AN: 604

GnomAD4 genome AF: 0.179 AC: 27222 AN: 152122 Hom.: 3509 Cov.: 32 AF XY: 0.171 AC XY: 12695 AN XY: 74390

African (AFR) AF: 0.358 AC: 14830 AN: 41434

American (AMR) AF: 0.0985 AC: 1506 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 471 AN: 3470

East Asian (EAS) AF: 0.0208 AC: 108 AN: 5186

South Asian (SAS) AF: 0.116 AC: 560 AN: 4826

European-Finnish (FIN) AF: 0.0572 AC: 606 AN: 10600

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.127 AC: 8619 AN: 67994

Other (OTH) AF: 0.168 AC: 356 AN: 2114

Alfa AF: 0.143 Hom.: 3865

Bravo AF: 0.190

Asia WGS AF: 0.111 AC: 387 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.49
DANN	Benign	0.44
PhyloP100		-0.037
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs260808; hg19: chr11-103909166;