Genetic Variant DDHD1:c.*3366_*3375dupACACACACAC (chr14-53043392-A-AGTGTGTGTGT) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001160148.2(DDHD1):c.*3366_*3375dupACACACACAC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.018 ( 18 hom., cov: 0)

Exomes 𝑓: 0.045 ( 0 hom. )

Consequence

DDHD1
NM_001160148.2 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.05

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

hereditary spastic paraplegia
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
hereditary spastic paraplegia 28
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet, Ambry Genetics

DDHD1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAdExome4 highest subpopulation (NFE) allele frequency = 0.0556 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDHD1	NM_001160148.2 link	c.3366_3375dupACACACACAC		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	ENST00000673822.2 link	c.3366_3375dupACACACACAC		3_prime_UTR_variant	Exon 13 of 13		NM_001160148.2	ENSP00000500986.2		Q8NEL9-1
DDHD1	ENST00000395606.5 link	c.3366_3375dupACACACACAC		3_prime_UTR_variant	Exon 13 of 13	2		ENSP00000378970.1		Q8NEL9-4

Frequencies

GnomAD3 genomes

AF:

0.0177

AC:

1987

AN:

112342

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00883

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00946

Gnomad ASJ

AF:

0.00833

Gnomad EAS

AF:

0.0356

Gnomad SAS

AF:

0.00878

Gnomad FIN

AF:

0.0429

Gnomad MID

AF:

0.00420

Gnomad NFE

AF:

0.0235

Gnomad OTH

AF:

0.0148

GnomAD4 exome

AF:

0.0455

AC:

AN:

Hom.:

Cov.:

AF XY:

0.0714

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0556

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0176

AC:

1984

AN:

112432

Hom.:

Cov.:

AF XY:

0.0173

AC XY:

932

AN XY:

53990

show subpopulations

African (AFR)

AF:

0.00878

AC:

319

AN:

36320

American (AMR)

AF:

0.00944

AC:

105

AN:

11122

Ashkenazi Jewish (ASJ)

AF:

0.00833

AC:

AN:

2760

East Asian (EAS)

AF:

0.0354

AC:

126

AN:

3562

South Asian (SAS)

AF:

0.00883

AC:

AN:

2832

European-Finnish (FIN)

AF:

0.0429

AC:

244

AN:

5690

Middle Eastern (MID)

AF:

0.00446

AC:

AN:

224

European-Non Finnish (NFE)

AF:

0.0235

AC:

1118

AN:

47642

Other (OTH)

AF:

0.0146

AC:

AN:

1574

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

166

249

332

415

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0129

Hom.:

108

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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14-53043392-A-AGTGTGTGTGT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over