rs138906273

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001160148.2(DDHD1):c.1524A>G(p.Gln508Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00182 in 1,613,696 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0015 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0019 ( 8 hom. )

Consequence

DDHD1
NM_001160148.2 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.74

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 14-53063185-T-C is Benign according to our data. Variant chr14-53063185-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 380535.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.74 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00148 (225/152330) while in subpopulation NFE AF = 0.00248 (169/68028). AF 95% confidence interval is 0.00218. There are 1 homozygotes in GnomAd4. There are 106 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDHD1	NM_001160148.2 link	c.1524A>G	p.Gln508Gln	synonymous_variant	Exon 7 of 13	ENST00000673822.2	NP_001153620.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDHD1	ENST00000673822.2 link	c.1524A>G	p.Gln508Gln	synonymous_variant	Exon 7 of 13		NM_001160148.2	ENSP00000500986.2

Frequencies

GnomAD3 genomes

AF:

0.00148

AC:

225

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00242

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00248

Gnomad OTH

AF:

0.000955

GnomAD2 exomes

AF:

0.00151

AC:

379

AN:

250882

AF XY:

0.00162

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.000926

Gnomad ASJ exome

AF:

0.00218

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000187

Gnomad NFE exome

AF:

0.00254

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.00185

AC:

2705

AN:

1461366

Hom.:

Cov.:

AF XY:

0.00180

AC XY:

1305

AN XY:

726998

show subpopulations

African (AFR)

AF:

0.000299

AC:

AN:

33466

American (AMR)

AF:

0.000783

AC:

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.00210

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39680

South Asian (SAS)

AF:

0.000684

AC:

AN:

86232

European-Finnish (FIN)

AF:

0.000377

AC:

AN:

53090

Middle Eastern (MID)

AF:

0.00173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00217

AC:

2410

AN:

1111894

Other (OTH)

AF:

0.00176

AC:

106

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

140

280

420

560

700

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

168

252

336

420

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00148

AC:

225

AN:

152330

Hom.:

Cov.:

AF XY:

0.00142

AC XY:

106

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.000168

AC:

AN:

41588

American (AMR)

AF:

0.00242

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00173

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.000622

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.0000942

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00248

AC:

169

AN:

68028

Other (OTH)

AF:

0.000945

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00197

Hom.:

Bravo

AF:

0.00151

EpiCase

AF:

0.00284

EpiControl

AF:

0.00273

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 18, 2019

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

DDHD1: BP4, BP7 -

Hereditary spastic paraplegia

Benign:1

Mar 30, 2021

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hereditary spastic paraplegia 28

Benign:1

Jan 30, 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

-0.53

CADD

Benign

9.2

(source)

DANN

Benign

0.80

PhyloP100

1.7

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over