rs55671452

chr14-53152762-TGCC-Tchr14-53152762-TGCC-TGCCGCCchr14-53152762-TGCC-TGCCGCCGCCchr14-53152762-TGCC-TGCCGCCGCCGCCchr14-53152762-TGCC-TGCCGCCGCCGCCGCCchr14-53152762-TGCC-TGCCGCCGCCGCCGCCGCCchr14-53152762-TGCC-TGCCGCCGCCGCCGCCGCCGCC

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PM4_Supporting

The NM_001160148.2(DDHD1):c.334_336del(p.Gly112del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000425 in 1,576,548 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000046 (0 hom.)
• Consequence: DDHD1 NM_001160148.2 inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.84

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_001160148.2. Strenght limited to Supporting due to length of the change: 1aa.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDHD1	NM_001160148.2	c.334_336del	p.Gly112del	inframe_deletion	1/13	ENST00000673822.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDHD1	ENST00000673822.2	c.334_336del	p.Gly112del	inframe_deletion	1/13		NM_001160148.2	A2
DDHD1	ENST00000357758.3	c.334_336del	p.Gly112del	inframe_deletion	1/12	1		P4
DDHD1	ENST00000395606.5	c.334_336del	p.Gly112del	inframe_deletion	1/13	2		A2

Frequencies

GnomAD3 genomes AF: 0.00000664 AC: 1 AN: 150570 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000148

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000463 AC: 66 AN: 1425978 Hom.: 0 AF XY: 0.0000467 AC XY: 33 AN XY: 707124

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000255

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000120

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000566

Gnomad4 OTH exome AF: 0.0000340

GnomAD4 genome AF: 0.00000664 AC: 1 AN: 150570 Hom.: 0 Cov.: 0 AF XY: 0.0000136 AC XY: 1 AN XY: 73430

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000148

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

LitVar

Other links and lift over

dbSNP: rs55671452; hg19: chr14-53619480;