14-53152762-TGCCGCC-TGCCGCCGCCGCC

Variant names:

• chr14-53152762-T-TGCCGCC
• rs55671452
• NM_001160148.2:c.331_336dupGGCGGC

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 2P and 16B. PM4 BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.972
• Publications: 7 publications found

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

ACMG classification

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDHD1	NM_001160148.2	c.331_336dupGGCGGC	p.Gly111_Gly112dup	conservative_inframe_insertion	Exon 1 of 13	ENST00000673822.2	NP_001153620.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDHD1	ENST00000673822.2	c.331_336dupGGCGGC	p.Gly111_Gly112dup	conservative_inframe_insertion	Exon 1 of 13		NM_001160148.2	ENSP00000500986.2

Frequencies

GnomAD3 genomes AF: 0.753 AC: 113312 AN: 150480 Hom.: 44177 Cov.: 0

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

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

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

GnomAD4 genome AF: 0.753 AC: 113368 AN: 150588 Hom.: 44193 Cov.: 0 AF XY: 0.757 AC XY: 55606 AN XY: 73504

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

Alfa AF: 0.775 Hom.: 4554

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Hereditary spastic paraplegia 28 Benign:2

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:2

Jun 11, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 04, 2016

GeneDx

Significance: Benign

Review Status: flagged submission

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.97
Mutation Taster		=84/16	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs55671452; hg19: chr14-53619480; COSMIC: COSV60356905; COSMIC: COSV60356905;