14-53152762-TGCCGCC-TGCCGCCGCCGCC

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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
DDHD1	ENST00000357758.3	c.331_336dupGGCGGC	p.Gly111_Gly112dup	conservative_inframe_insertion	Exon 1 of 12	1		ENSP00000350401.3
DDHD1	ENST00000395606.5	c.331_336dupGGCGGC	p.Gly111_Gly112dup	conservative_inframe_insertion	Exon 1 of 13	2		ENSP00000378970.1
DDHD1	ENST00000673930.1	c.-153_-148dupGGCGGC		upstream_gene_variant				ENSP00000501087.1

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

GnomAD3 exomes AF: 0.834 AC: 155876 AN: 187002 Hom.: 65883 AF XY: 0.838 AC XY: 86660 AN XY: 103428

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 SAS exome AF: 0.873

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

Gnomad4 AFR exome AF: 0.512

Gnomad4 AMR exome AF: 0.869

Gnomad4 ASJ exome AF: 0.781

Gnomad4 EAS exome AF: 0.941

Gnomad4 SAS exome AF: 0.874

Gnomad4 FIN exome AF: 0.822

Gnomad4 NFE exome AF: 0.830

Gnomad4 OTH exome AF: 0.813

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

Gnomad4 AFR AF: 0.525

Gnomad4 AMR AF: 0.828

Gnomad4 ASJ AF: 0.795

Gnomad4 EAS AF: 0.959

Gnomad4 SAS AF: 0.879

Gnomad4 FIN AF: 0.820

Gnomad4 NFE AF: 0.836

Gnomad4 OTH AF: 0.779

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

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 v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs55671452; hg19: chr14-53619480;