14-53063029-CA-AG

Variant names:

• chr14-53063029-CA-AG
• NM_001160148.2:c.1679_1680delTGinsCT
• DDHD1 p.Leu560Pro

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001160148.2(DDHD1):​c.1679_1680delTGinsCT​(p.Leu560Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DDHD1 NM_001160148.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.31
• Publications: 0 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 Gene-Disease associations (from GenCC):

• hereditary spastic paraplegia

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• hereditary spastic paraplegia 28

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet, G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDHD1	NM_001160148.2	MANE Select	c.1679_1680delTGinsCT	p.Leu560Pro	missense	N/A	NP_001153620.1	Q8NEL9-1
	DDHD1	NM_001160147.2		c.1700_1701delTGinsCT	p.Leu567Pro	missense	N/A	NP_001153619.1	Q8NEL9-4
	DDHD1	NM_030637.3		c.1679_1680delTGinsCT	p.Leu560Pro	missense	N/A	NP_085140.2	Q8NEL9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDHD1	ENST00000673822.2	MANE Select	c.1679_1680delTGinsCT	p.Leu560Pro	missense	N/A	ENSP00000500986.2	Q8NEL9-1
	DDHD1	ENST00000357758.3	TSL:1	c.1679_1680delTGinsCT	p.Leu560Pro	missense	N/A	ENSP00000350401.3	Q8NEL9-2
	DDHD1	ENST00000556027.5	TSL:1	n.2270_2271delTGinsCT		non_coding_transcript_exon	Exon 4 of 9

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.3

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr14-53529747;