NM_001160148.2:c.331_336delGGCGGC

Variant names:

• chr14-53152762-TGCCGCC-T
• rs55671452
• NM_001160148.2:c.331_336delGGCGGC

Variant summary

Our verdict is Uncertain significance. The variant received 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
• 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-DT (HGNC:55441): (DDHD1 divergent transcript)

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

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

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.331_336delGGCGGC	p.Gly111_Gly112del	conservative_inframe_deletion	Exon 1 of 13	NP_001153620.1	Q8NEL9-1
	DDHD1	NM_001160147.2		c.331_336delGGCGGC	p.Gly111_Gly112del	conservative_inframe_deletion	Exon 1 of 13	NP_001153619.1	Q8NEL9-4
	DDHD1	NM_030637.3		c.331_336delGGCGGC	p.Gly111_Gly112del	conservative_inframe_deletion	Exon 1 of 12	NP_085140.2	Q8NEL9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDHD1	ENST00000673822.2	MANE Select	c.331_336delGGCGGC	p.Gly111_Gly112del	conservative_inframe_deletion	Exon 1 of 13	ENSP00000500986.2	Q8NEL9-1
	DDHD1	ENST00000357758.3	TSL:1	c.331_336delGGCGGC	p.Gly111_Gly112del	conservative_inframe_deletion	Exon 1 of 12	ENSP00000350401.3	Q8NEL9-2
	DDHD1	ENST00000907176.1		c.331_336delGGCGGC	p.Gly111_Gly112del	conservative_inframe_deletion	Exon 1 of 15	ENSP00000577235.1

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

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

American (AMR) AF: 0.00 AC: 0 AN: 39264

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

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

South Asian (SAS) AF: 0.00 AC: 0 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: 0.00000548 AC: 6 AN: 1094614

Other (OTH) AF: 0.00 AC: 0 AN: 58888

GnomAD4 genome Cov.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Hereditary spastic paraplegia 28 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.7

Splicing

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

Other links and lift over

dbSNP: rs55671452; hg19: chr14-53619480;