rs260808

Positions:

• chr11-104038438-C-A

Variant summary

Our verdict is Benign. Variant got -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

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 Benign. Variant got -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/exons	MANE	Protein	UniProt
DDI1	NM_001001711.3	c.*425C>A		3_prime_UTR_variant	1/1	ENST00000302259.5	NP_001001711.1
PDGFD	NM_025208.5	c.125-38183G>T		intron_variant		ENST00000393158.7	NP_079484.1
PDGFD	NM_033135.4	c.125-38201G>T		intron_variant			NP_149126.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDI1	ENST00000302259.5	c.*425C>A		3_prime_UTR_variant	1/1	6	NM_001001711.3	ENSP00000302805.3
PDGFD	ENST00000393158.7	c.125-38183G>T		intron_variant		1	NM_025208.5	ENSP00000376865.2
PDGFD	ENST00000302251.9	c.125-38201G>T		intron_variant		1		ENSP00000302193.5

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

Gnomad4 AFR exome AF: 0.314

Gnomad4 AMR exome AF: 0.0863

Gnomad4 ASJ exome AF: 0.158

Gnomad4 EAS exome AF: 0.00822

Gnomad4 SAS exome AF: 0.110

Gnomad4 FIN exome AF: 0.0614

Gnomad4 NFE exome AF: 0.115

Gnomad4 OTH exome AF: 0.0927

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

Gnomad4 AFR AF: 0.358

Gnomad4 AMR AF: 0.0985

Gnomad4 ASJ AF: 0.136

Gnomad4 EAS AF: 0.0208

Gnomad4 SAS AF: 0.116

Gnomad4 FIN AF: 0.0572

Gnomad4 NFE AF: 0.127

Gnomad4 OTH AF: 0.168

Alfa AF: 0.138 Hom.: 2582

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

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

LitVar

Other links and lift over

dbSNP: rs260808; hg19: chr11-103909166;