11-104037287-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_001001711.3(DDI1):c.465C>T(p.His155=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00374 in 1,613,264 control chromosomes in the GnomAD database, including 194 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.019 (102 hom., cov: 32)
  • Exomes 𝑓: 0.0022 (92 hom.)
• Consequence: DDI1 NM_001001711.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.75

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 11-104037287-C-T is Benign according to our data. Variant chr11-104037287-C-T is described in ClinVar as [Benign]. Clinvar id is 785380.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.75 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0629 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDI1	NM_001001711.3	c.465C>T	p.His155=	synonymous_variant	1/1	ENST00000302259.5
PDGFD	NM_025208.5	c.125-37032G>A		intron_variant		ENST00000393158.7
PDGFD	NM_033135.4	c.125-37050G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDI1	ENST00000302259.5	c.465C>T	p.His155=	synonymous_variant	1/1		NM_001001711.3	P1
PDGFD	ENST00000393158.7	c.125-37032G>A		intron_variant		1	NM_025208.5	P1
PDGFD	ENST00000302251.9	c.125-37050G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.0189 AC: 2883 AN: 152208 Hom.: 101 Cov.: 32

Gnomad AFR AF: 0.0650

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00772

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000617

Gnomad OTH AF: 0.0115

GnomAD3 exomes AF: 0.00510 AC: 1273 AN: 249622 Hom.: 41 AF XY: 0.00362 AC XY: 489 AN XY: 134988

Gnomad AFR exome AF: 0.0677

Gnomad AMR exome AF: 0.00327

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000654

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000437

Gnomad OTH exome AF: 0.00230

GnomAD4 exome AF: 0.00216 AC: 3150 AN: 1460938 Hom.: 92 Cov.: 31 AF XY: 0.00186 AC XY: 1351 AN XY: 726564

Gnomad4 AFR exome AF: 0.0635

Gnomad4 AMR exome AF: 0.00374

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000696

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000542

Gnomad4 OTH exome AF: 0.00398

GnomAD4 genome AF: 0.0190 AC: 2888 AN: 152326 Hom.: 102 Cov.: 32 AF XY: 0.0182 AC XY: 1357 AN XY: 74484

Gnomad4 AFR AF: 0.0650

Gnomad4 AMR AF: 0.00771

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000617

Gnomad4 OTH AF: 0.0114

Alfa AF: 0.00688 Hom.: 12

Bravo AF: 0.0212

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.000491

EpiControl AF: 0.000533

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 26, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
Cadd	Benign	0.42
Dann	Benign	0.76

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: rs77123941; hg19: chr11-103908015; COSMIC: COSV56374721; COSMIC: COSV56374721;