14-53152762-TGCCGCC-TGCC

Variant names:

• chr14-53152762-TGCC-T
• rs55671452
• NM_001160148.2:c.334_336delGGC

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PM4_Supporting

The NM_001160148.2(DDHD1):​c.334_336delGGC​(p.Gly112del) variant causes a conservative 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 conservative_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.84
• 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: Uncertain_significance. The variant received 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 rank	MANE	Protein	UniProt
DDHD1	NM_001160148.2	c.334_336delGGC	p.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.334_336delGGC	p.Gly112del	conservative_inframe_deletion	Exon 1 of 13		NM_001160148.2	ENSP00000500986.2

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

African (AFR) AF: 0.00 AC: 0 AN: 32884

American (AMR) AF: 0.0000255 AC: 1 AN: 39262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24980

East Asian (EAS) AF: 0.00 AC: 0 AN: 38440

South Asian (SAS) AF: 0.0000120 AC: 1 AN: 83114

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49196

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4600

European-Non Finnish (NFE) AF: 0.0000566 AC: 62 AN: 1094614

Other (OTH) AF: 0.0000340 AC: 2 AN: 58888

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

African (AFR) AF: 0.00 AC: 0 AN: 40934

American (AMR) AF: 0.00 AC: 0 AN: 15190

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3458

East Asian (EAS) AF: 0.00 AC: 0 AN: 4934

South Asian (SAS) AF: 0.00 AC: 0 AN: 4774

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10444

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000148 AC: 1 AN: 67546

Other (OTH) AF: 0.00 AC: 0 AN: 2076

Alfa AF: 0.00 Hom.: 4554

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.8
Mutation Taster		=81/19	polymorphism

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

Other links and lift over

dbSNP: rs55671452; hg19: chr14-53619480;