11-104037356-C-T

Position:

• chr11-104037356-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001001711.3(DDI1):​c.534C>T​(p.Thr178Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00258 in 1,614,088 control chromosomes in the GnomAD database, including 97 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.014 (52 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (45 hom.)
• Consequence: DDI1 NM_001001711.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.38

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 11-104037356-C-T is Benign according to our data. Variant chr11-104037356-C-T is described in ClinVar as [Benign]. Clinvar id is 777651.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.38 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0141 (2143/152318) while in subpopulation AFR AF= 0.0485 (2018/41570). AF 95% confidence interval is 0.0468. There are 52 homozygotes in gnomad4. There are 1025 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 52 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDI1	NM_001001711.3	c.534C>T	p.Thr178Thr	synonymous_variant	1/1	ENST00000302259.5	NP_001001711.1
PDGFD	NM_025208.5	c.125-37101G>A		intron_variant		ENST00000393158.7	NP_079484.1
PDGFD	NM_033135.4	c.125-37119G>A		intron_variant			NP_149126.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDI1	ENST00000302259.5	c.534C>T	p.Thr178Thr	synonymous_variant	1/1	6	NM_001001711.3	ENSP00000302805.3
PDGFD	ENST00000393158.7	c.125-37101G>A		intron_variant		1	NM_025208.5	ENSP00000376865.2
PDGFD	ENST00000302251.9	c.125-37119G>A		intron_variant		1		ENSP00000302193.5

Frequencies

GnomAD3 genomes AF: 0.0140 AC: 2134 AN: 152200 Hom.: 52 Cov.: 32

Gnomad AFR AF: 0.0485

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00648

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.0105

GnomAD3 exomes AF: 0.00358 AC: 896 AN: 250450 Hom.: 20 AF XY: 0.00265 AC XY: 359 AN XY: 135502

Gnomad AFR exome AF: 0.0502

Gnomad AMR exome AF: 0.00188

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: 0.0000708

Gnomad OTH exome AF: 0.00164

GnomAD4 exome AF: 0.00138 AC: 2020 AN: 1461770 Hom.: 45 Cov.: 31 AF XY: 0.00116 AC XY: 846 AN XY: 727190

Gnomad4 AFR exome AF: 0.0505

Gnomad4 AMR exome AF: 0.00233

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000580

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000288

Gnomad4 OTH exome AF: 0.00301

GnomAD4 genome AF: 0.0141 AC: 2143 AN: 152318 Hom.: 52 Cov.: 32 AF XY: 0.0138 AC XY: 1025 AN XY: 74480

Gnomad4 AFR AF: 0.0485

Gnomad4 AMR AF: 0.00647

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.0104

Alfa AF: 0.00731 Hom.: 12

Bravo AF: 0.0165

Asia WGS AF: 0.00289 AC: 10 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 05, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.024
DANN	Benign	0.73

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: rs260807; hg19: chr11-103908084;