Variant 14-53046607-ACTT-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_001160148.2(DDHD1):c.*158_*160del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0365 in 467,758 control chromosomes in the GnomAD database, including 1,201 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.072 ( 998 hom., cov: 31)

Exomes 𝑓: 0.020 ( 203 hom. )

Consequence

DDHD1
NM_001160148.2 3_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.132

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 -10 ACMG points.

BP6

Variant 14-53046607-ACTT-A is Benign according to our data. Variant chr14-53046607-ACTT-A is described in ClinVar as [Benign]. Clinvar id is 1183899.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.212 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.158_160del		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.158_160del		3_prime_UTR_variant	13/13		NM_001160148.2	ENSP00000500986	A2	Q8NEL9-1

Frequencies

GnomAD3 genomes

AF:

0.0718

AC:

10893

AN:

151722

Hom.:

997

Cov.:

show subpopulations

Gnomad AFR

AF:

0.216

Gnomad AMI

AF:

0.116

Gnomad AMR

AF:

0.0387

Gnomad ASJ

AF:

0.0337

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00685

Gnomad FIN

AF:

0.00370

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0147

Gnomad OTH

AF:

0.0579

GnomAD4 exome

AF:

0.0195

AC:

6176

AN:

315916

Hom.:

203

AF XY:

0.0185

AC XY:

2981

AN XY:

161482

show subpopulations

Gnomad4 AFR exome

AF:

0.210

Gnomad4 AMR exome

AF:

0.0284

Gnomad4 ASJ exome

AF:

0.0400

Gnomad4 EAS exome

AF:

0.0000871

Gnomad4 SAS exome

AF:

0.00703

Gnomad4 FIN exome

AF:

0.00304

Gnomad4 NFE exome

AF:

0.0151

Gnomad4 OTH exome

AF:

0.0325

GnomAD4 genome

AF:

0.0719

AC:

10910

AN:

151842

Hom.:

998

Cov.:

AF XY:

0.0696

AC XY:

5162

AN XY:

74192

show subpopulations

Gnomad4 AFR

AF:

0.215

Gnomad4 AMR

AF:

0.0385

Gnomad4 ASJ

AF:

0.0337

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00686

Gnomad4 FIN

AF:

0.00370

Gnomad4 NFE

AF:

0.0147

Gnomad4 OTH

AF:

0.0568

Alfa

AF:

0.0494

Hom.:

Bravo

AF:

0.0806

Asia WGS

AF:

0.0150

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 31, 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