rs55671452

Variant names:

• chr14-53152762-TGCCGCC-T
• NM_001160148.2:c.331_336delGGCGGC

Your query was ambiguous. Multiple possible variants found:

• chr14-53152762-TGCCGCC-T
• chr14-53152762-TGCCGCC-TGCC
• chr14-53152762-TGCCGCC-TGCCGCCGCC
• chr14-53152762-TGCCGCC-TGCCGCCGCCGCC
• chr14-53152762-TGCCGCC-TGCCGCCGCCGCCGCC
• chr14-53152762-TGCCGCC-TGCCGCCGCCGCCGCCGCC
• chr14-53152762-TGCCGCC-TGCCGCCGCCGCCGCCGCCGCC
• chr14-53152762-TGCCGCC-TGCCGCCGCCGCCGCCGCCGCCGCC

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM4

The NM_001160148.2(DDHD1):​c.331_336delGGCGGC​(p.Gly111_Gly112del) variant causes a conservative inframe deletion change. The variant allele was found at a frequency of 0.00000421 in 1,425,980 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0000042 (0 hom.)
• Consequence: DDHD1 NM_001160148.2 conservative_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.71

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 Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_001160148.2.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDHD1	NM_001160148.2	c.331_336delGGCGGC	p.Gly111_Gly112del	conservative_inframe_deletion	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_336delGGCGGC	p.Gly111_Gly112del	conservative_inframe_deletion	Exon 1 of 13		NM_001160148.2	ENSP00000500986.2
DDHD1	ENST00000357758.3	c.331_336delGGCGGC	p.Gly111_Gly112del	conservative_inframe_deletion	Exon 1 of 12	1		ENSP00000350401.3
DDHD1	ENST00000395606.5	c.331_336delGGCGGC	p.Gly111_Gly112del	conservative_inframe_deletion	Exon 1 of 13	2		ENSP00000378970.1
DDHD1	ENST00000673930.1	c.-153_-148delGGCGGC		upstream_gene_variant				ENSP00000501087.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000421 AC: 6 AN: 1425980 Hom.: 0 AF XY: 0.00000283 AC XY: 2 AN XY: 707124

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000548

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hereditary spastic paraplegia 28 Uncertain:1

Apr 24, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has not been reported in the literature in individuals affected with DDHD1-related conditions. This variant is not present in population databases (gnomAD no frequency). This variant, c.331_336del, results in the deletion of 2 amino acid(s) of the DDHD1 protein (p.Gly111_Gly112del), but otherwise preserves the integrity of the reading frame. -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-53619480;