rs180742508

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001160148.2(DDHD1):c.1503+10A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00278 in 1,453,538 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0029 ( 4 hom. )

Consequence

DDHD1
NM_001160148.2 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.10

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 14-53072587-T-A is Benign according to our data. Variant chr14-53072587-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 238598.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-53072587-T-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00179 (273/152178) while in subpopulation NFE AF= 0.00314 (213/67926). AF 95% confidence interval is 0.00279. There are 0 homozygotes in gnomad4. There are 119 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDHD1	NM_001160148.2 link	c.1503+10A>T		intron_variant	Intron 6 of 12	ENST00000673822.2	NP_001153620.1	Q8NEL9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDHD1	ENST00000673822.2 link	c.1503+10A>T		intron_variant	Intron 6 of 12		NM_001160148.2	ENSP00000500986.2		Q8NEL9-1

Frequencies

GnomAD3 genomes

AF:

0.00180

AC:

273

AN:

152060

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000434

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000328

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00254

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00314

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00280

AC:

609

AN:

217404

Hom.:

AF XY:

0.00281

AC XY:

333

AN XY:

118482

show subpopulations

Gnomad AFR exome

AF:

0.000483

Gnomad AMR exome

AF:

0.000282

Gnomad ASJ exome

AF:

0.00204

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00213

Gnomad NFE exome

AF:

0.00511

Gnomad OTH exome

AF:

0.00157

GnomAD4 exome

AF:

0.00289

AC:

3761

AN:

1301360

Hom.:

Cov.:

AF XY:

0.00290

AC XY:

1863

AN XY:

643400

show subpopulations

Gnomad4 AFR exome

AF:

0.000370

Gnomad4 AMR exome

AF:

0.000257

Gnomad4 ASJ exome

AF:

0.00219

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00286

Gnomad4 NFE exome

AF:

0.00341

Gnomad4 OTH exome

AF:

0.00223

GnomAD4 genome

AF:

0.00179

AC:

273

AN:

152178

Hom.:

Cov.:

AF XY:

0.00160

AC XY:

119

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.000433

Gnomad4 AMR

AF:

0.000328

Gnomad4 ASJ

AF:

0.00288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00254

Gnomad4 NFE

AF:

0.00314

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00108

Hom.:

Bravo

AF:

0.00168

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 05, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:1

Jun 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

DDHD1: BS2 -

Hereditary spastic paraplegia 28

Benign:1

Jan 26, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.32

DANN

Benign

0.60

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over