Genetic Variant DDHD1:c.*156delA (chr14-53046611-CT-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BS1

The NM_001160148.2(DDHD1):c.*156delA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0103 in 404,286 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.015 ( 0 hom. )

Consequence

DDHD1
NM_001160148.2 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.71

Variant links:

Genes affected

DDHD1 (HGNC:19714): (DDHD domain containing 1) This gene is a member of the intracellular phospholipase A1 gene family. The protein encoded by this gene preferentially hydrolyzes phosphatidic acid. It is a cytosolic protein with some mitochondrial localization, and is thought to be involved in the regulation of mitochondrial dynamics. Overexpression of this gene causes fragmentation of the tubular structures in mitochondria, while depletion of the gene results in mitochondrial tubule elongation. Deletion of this gene in male mice caused fertility defects, resulting from disruption in the organization of the mitochondria during spermiogenesis. In humans, mutations in this gene have been associated with hereditary spastic paraplegia (HSP), also known as Strumpell-Lorrain disease, or, familial spastic paraparesis (FSP). This inherited disorder is characterized by progressive weakness and spasticity of the legs. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Aug 2015]

DDHD1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000388 (50/128904) while in subpopulation EAS AF= 0.000785 (4/5098). AF 95% confidence interval is 0.000346. There are 0 homozygotes in gnomad4. There are 32 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDHD1	NM_001160148.2 link	c.*156delA		3_prime_UTR_variant	Exon 13 of 13	ENST00000673822.2	NP_001153620.1	Q8NEL9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDHD1	ENST00000673822 link	c.*156delA		3_prime_UTR_variant	Exon 13 of 13		NM_001160148.2	ENSP00000500986.2		Q8NEL9-1

Frequencies

GnomAD3 genomes

AF:

0.000388

AC:

AN:

128840

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000359

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000147

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000782

Gnomad SAS

AF:

0.000217

Gnomad FIN

AF:

0.000208

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000478

Gnomad OTH

AF:

0.000553

GnomAD4 exome

AF:

0.0149

AC:

4113

AN:

275382

Hom.:

Cov.:

AF XY:

0.0154

AC XY:

2159

AN XY:

140294

show subpopulations

Gnomad4 AFR exome

AF:

0.0138

Gnomad4 AMR exome

AF:

0.0175

Gnomad4 ASJ exome

AF:

0.0135

Gnomad4 EAS exome

AF:

0.0133

Gnomad4 SAS exome

AF:

0.0168

Gnomad4 FIN exome

AF:

0.0111

Gnomad4 NFE exome

AF:

0.0156

Gnomad4 OTH exome

AF:

0.0149

GnomAD4 genome

AF:

0.000388

AC:

AN:

128904

Hom.:

Cov.:

AF XY:

0.000507

AC XY:

AN XY:

63094

show subpopulations

Gnomad4 AFR

AF:

0.000358

Gnomad4 AMR

AF:

0.000147

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000785

Gnomad4 SAS

AF:

0.000218

Gnomad4 FIN

AF:

0.000208

Gnomad4 NFE

AF:

0.000478

Gnomad4 OTH

AF:

0.000547

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over