14-53152762-TGCCGCC-TGCCGCCGCCGCCGCC

Variant names:

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM4BP6_Very_StrongBS1BS2

The NM_001160148.2(DDHD1):c.328_336dupGGCGGCGGC(p.Gly110_Gly112dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00446 in 1,576,608 control chromosomes in the GnomAD database, including 142 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0096 ( 36 hom., cov: 0)

Exomes 𝑓: 0.0039 ( 106 hom. )

Consequence

DDHD1
NM_001160148.2 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.972

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_001160148.2.

BP6

Variant 14-53152762-T-TGCCGCCGCC is Benign according to our data. Variant chr14-53152762-T-TGCCGCCGCC is described in ClinVar as [Likely_benign]. Clinvar id is 415257.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00964 (1452/150660) while in subpopulation AFR AF= 0.0122 (500/41052). AF 95% confidence interval is 0.0113. There are 36 homozygotes in gnomad4. There are 881 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 36 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDHD1	NM_001160148.2 link	c.328_336dupGGCGGCGGC	p.Gly110_Gly112dup	conservative_inframe_insertion	Exon 1 of 13	ENST00000673822.2	NP_001153620.1	Q8NEL9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DDHD1	ENST00000673822.2 link	c.328_336dupGGCGGCGGC	p.Gly110_Gly112dup	conservative_inframe_insertion	Exon 1 of 13		NM_001160148.2	ENSP00000500986.2	Q8NEL9-1
DDHD1	ENST00000357758.3 link	c.328_336dupGGCGGCGGC	p.Gly110_Gly112dup	conservative_inframe_insertion	Exon 1 of 12	1		ENSP00000350401.3	Q8NEL9-2
DDHD1	ENST00000395606.5 link	c.328_336dupGGCGGCGGC	p.Gly110_Gly112dup	conservative_inframe_insertion	Exon 1 of 13	2		ENSP00000378970.1	Q8NEL9-4
DDHD1	ENST00000673930.1 link	c.-156_-148dupGGCGGCGGC		upstream_gene_variant				ENSP00000501087.1	A0A669KB51

Frequencies

GnomAD3 genomes

AF:

0.00964

AC:

1452

AN:

150552

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0122

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.000868

Gnomad EAS

AF:

0.00851

Gnomad SAS

AF:

0.00230

Gnomad FIN

AF:

0.0690

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00224

Gnomad OTH

AF:

0.00337

GnomAD3 exomes

AF:

0.00886

AC:

1657

AN:

187002

Hom.:

AF XY:

0.00796

AC XY:

823

AN XY:

103428

show subpopulations

Gnomad AFR exome

AF:

0.0120

Gnomad AMR exome

AF:

0.00121

Gnomad ASJ exome

AF:

0.00126

Gnomad EAS exome

AF:

0.00889

Gnomad SAS exome

AF:

0.00212

Gnomad FIN exome

AF:

0.0642

Gnomad NFE exome

AF:

0.00261

Gnomad OTH exome

AF:

0.00438

GnomAD4 exome

AF:

0.00392

AC:

5587

AN:

1425948

Hom.:

106

Cov.:

111

AF XY:

0.00378

AC XY:

2670

AN XY:

707108

show subpopulations

Gnomad4 AFR exome

AF:

0.0124

Gnomad4 AMR exome

AF:

0.00135

Gnomad4 ASJ exome

AF:

0.00140

Gnomad4 EAS exome

AF:

0.00736

Gnomad4 SAS exome

AF:

0.00231

Gnomad4 FIN exome

AF:

0.0637

Gnomad4 NFE exome

AF:

0.00112

Gnomad4 OTH exome

AF:

0.00421

GnomAD4 genome

AF:

0.00964

AC:

1452

AN:

150660

Hom.:

Cov.:

AF XY:

0.0120

AC XY:

881

AN XY:

73534

show subpopulations

Gnomad4 AFR

AF:

0.0122

Gnomad4 AMR

AF:

0.00118

Gnomad4 ASJ

AF:

0.000868

Gnomad4 EAS

AF:

0.00854

Gnomad4 SAS

AF:

0.00231

Gnomad4 FIN

AF:

0.0690

Gnomad4 NFE

AF:

0.00224

Gnomad4 OTH

AF:

0.00334

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Feb 26, 2018

GeneDx

Significance: 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. -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:2

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Apr 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

DDHD1: PM4, BS1, BS2 -

Hereditary spastic paraplegia 28

Benign:1

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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