NM_001160148.2:c.331_336dupGGCGGC

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 2P and 16B. PM4BP6_Very_StrongBA1

The NM_001160148.2(DDHD1):c.331_336dupGGCGGC(p.Gly111_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 0.82 in 1,576,386 control chromosomes in the GnomAD database, including 533,603 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.75 ( 44193 hom., cov: 0)

Exomes 𝑓: 0.83 ( 489410 hom. )

Consequence

DDHD1
NM_001160148.2 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.972

Publications

7 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 links:

DDHD1-DT (HGNC:55441): (DDHD1 divergent transcript)

DDHD1-DT links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_001160148.2.

BP6

Variant 14-53152762-T-TGCCGCC is Benign according to our data. Variant chr14-53152762-T-TGCCGCC is described in ClinVar as Benign. ClinVar VariationId is 221131.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.936 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001160148.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DDHD1	NM_001160148.2	MANE Select	c.331_336dupGGCGGC	p.Gly111_Gly112dup	conservative_inframe_insertion	Exon 1 of 13	NP_001153620.1
DDHD1	NM_001160147.2		c.331_336dupGGCGGC	p.Gly111_Gly112dup	conservative_inframe_insertion	Exon 1 of 13	NP_001153619.1
DDHD1	NM_030637.3		c.331_336dupGGCGGC	p.Gly111_Gly112dup	conservative_inframe_insertion	Exon 1 of 12	NP_085140.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DDHD1	ENST00000673822.2	MANE Select	c.331_336dupGGCGGC	p.Gly111_Gly112dup	conservative_inframe_insertion	Exon 1 of 13	ENSP00000500986.2
DDHD1	ENST00000357758.3	TSL:1	c.331_336dupGGCGGC	p.Gly111_Gly112dup	conservative_inframe_insertion	Exon 1 of 12	ENSP00000350401.3
DDHD1	ENST00000395606.5	TSL:2	c.331_336dupGGCGGC	p.Gly111_Gly112dup	conservative_inframe_insertion	Exon 1 of 13	ENSP00000378970.1

Frequencies

GnomAD3 genomes

AF:

0.753

AC:

113312

AN:

150480

Hom.:

44177

Cov.:

show subpopulations

Gnomad AFR

AF:

0.525

Gnomad AMI

AF:

0.845

Gnomad AMR

AF:

0.828

Gnomad ASJ

AF:

0.795

Gnomad EAS

AF:

0.958

Gnomad SAS

AF:

0.878

Gnomad FIN

AF:

0.820

Gnomad MID

AF:

0.794

Gnomad NFE

AF:

0.836

Gnomad OTH

AF:

0.778

GnomAD2 exomes

AF:

0.834

AC:

155876

AN:

187002

AF XY:

0.838

show subpopulations

Gnomad AFR exome

AF:

0.503

Gnomad AMR exome

AF:

0.877

Gnomad ASJ exome

AF:

0.778

Gnomad EAS exome

AF:

0.961

Gnomad FIN exome

AF:

0.820

Gnomad NFE exome

AF:

0.836

Gnomad OTH exome

AF:

0.819

GnomAD4 exome

AF:

0.827

AC:

1179127

AN:

1425798

Hom.:

489410

Cov.:

111

AF XY:

0.830

AC XY:

586736

AN XY:

707038

show subpopulations

African (AFR)

AF:

0.512

AC:

16820

AN:

32864

American (AMR)

AF:

0.869

AC:

34094

AN:

39232

Ashkenazi Jewish (ASJ)

AF:

0.781

AC:

19502

AN:

24972

East Asian (EAS)

AF:

0.941

AC:

36180

AN:

38438

South Asian (SAS)

AF:

0.874

AC:

72592

AN:

83094

European-Finnish (FIN)

AF:

0.822

AC:

40438

AN:

49176

Middle Eastern (MID)

AF:

0.804

AC:

3697

AN:

4600

European-Non Finnish (NFE)

AF:

0.830

AC:

907961

AN:

1094544

Other (OTH)

AF:

0.813

AC:

47843

AN:

58878

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

12995

25989

38984

51978

64973

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20760

41520

62280

83040

103800

<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:

0.753

AC:

113368

AN:

150588

Hom.:

44193

Cov.:

AF XY:

0.757

AC XY:

55606

AN XY:

73504

show subpopulations

African (AFR)

AF:

0.525

AC:

21508

AN:

41006

American (AMR)

AF:

0.828

AC:

12596

AN:

15206

Ashkenazi Jewish (ASJ)

AF:

0.795

AC:

2748

AN:

3456

East Asian (EAS)

AF:

0.959

AC:

4714

AN:

4918

South Asian (SAS)

AF:

0.879

AC:

4187

AN:

4762

European-Finnish (FIN)

AF:

0.820

AC:

8559

AN:

10434

Middle Eastern (MID)

AF:

0.796

AC:

234

AN:

294

European-Non Finnish (NFE)

AF:

0.836

AC:

56431

AN:

67518

Other (OTH)

AF:

0.779

AC:

1634

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

1229

2458

3687

4916

6145

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

832

1664

2496

3328

4160

<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:

0.775

Hom.:

4554

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hereditary spastic paraplegia 28

Benign:2

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not provided

Benign:2

Mar 04, 2016

GeneDx

Significance:Benign

Review Status:flagged submission

Collection Method:clinical testing

Jun 11, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.97

Mutation Taster

=84/16

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over