Variant 14-53046760-AAG-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001160148.2(DDHD1):c.*6_*7del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.842 in 1,573,544 control chromosomes in the GnomAD database, including 558,594 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.84 ( 52491 hom., cov: 0)

Exomes 𝑓: 0.84 ( 506103 hom. )

Consequence

DDHD1
NM_001160148.2 3_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.09

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 -16 ACMG points.

BP6

Variant 14-53046760-AAG-A is Benign according to our data. Variant chr14-53046760-AAG-A is described in ClinVar as [Benign]. Clinvar id is 1255133.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-53046760-AAG-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.958 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDHD1	NM_001160148.2 linkuse as main transcript	c.6_7del		3_prime_UTR_variant	13/13	ENST00000673822.2	NP_001153620.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDHD1	ENST00000673822.2 linkuse as main transcript	c.6_7del		3_prime_UTR_variant	13/13		NM_001160148.2	ENSP00000500986	A2	Q8NEL9-1

Frequencies

GnomAD3 genomes

AF:

0.840

AC:

125810

AN:

149804

Hom.:

52438

Cov.:

show subpopulations

Gnomad AFR

AF:

0.803

Gnomad AMI

AF:

0.937

Gnomad AMR

AF:

0.861

Gnomad ASJ

AF:

0.806

Gnomad EAS

AF:

0.980

Gnomad SAS

AF:

0.884

Gnomad FIN

AF:

0.891

Gnomad MID

AF:

0.823

Gnomad NFE

AF:

0.835

Gnomad OTH

AF:

0.842

GnomAD3 exomes

AF:

0.860

AC:

192694

AN:

224068

Hom.:

83269

AF XY:

0.859

AC XY:

104584

AN XY:

121750

show subpopulations

Gnomad AFR exome

AF:

0.776

Gnomad AMR exome

AF:

0.904

Gnomad ASJ exome

AF:

0.806

Gnomad EAS exome

AF:

0.977

Gnomad SAS exome

AF:

0.880

Gnomad FIN exome

AF:

0.889

Gnomad NFE exome

AF:

0.837

Gnomad OTH exome

AF:

0.847

GnomAD4 exome

AF:

0.842

AC:

1199228

AN:

1423622

Hom.:

506103

AF XY:

0.844

AC XY:

597003

AN XY:

707736

show subpopulations

Gnomad4 AFR exome

AF:

0.808

Gnomad4 AMR exome

AF:

0.899

Gnomad4 ASJ exome

AF:

0.803

Gnomad4 EAS exome

AF:

0.988

Gnomad4 SAS exome

AF:

0.883

Gnomad4 FIN exome

AF:

0.889

Gnomad4 NFE exome

AF:

0.832

Gnomad4 OTH exome

AF:

0.840

GnomAD4 genome

AF:

0.840

AC:

125922

AN:

149922

Hom.:

52491

Cov.:

AF XY:

0.844

AC XY:

61816

AN XY:

73232

show subpopulations

Gnomad4 AFR

AF:

0.803

Gnomad4 AMR

AF:

0.861

Gnomad4 ASJ

AF:

0.806

Gnomad4 EAS

AF:

0.980

Gnomad4 SAS

AF:

0.885

Gnomad4 FIN

AF:

0.891

Gnomad4 NFE

AF:

0.835

Gnomad4 OTH

AF:

0.842

Alfa

AF:

0.836

Hom.:

6515

Bravo

AF:

0.824

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hereditary spastic paraplegia 28

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 11, 2018

- -

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over