14-53152762-TGCCGCC-TGCCGCCGCCGCCGCCGCC

Variant names:

• chr14-53152762-T-TGCCGCCGCCGCC
• rs55671452
• NM_001160148.2:c.325_336dupGGCGGCGGCGGC

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM4 BP6_Very_Strong BS1 BS2

The NM_001160148.2(DDHD1):​c.325_336dupGGCGGCGGCGGC​(p.Gly112_Ser113insGlyGlyGlyGly) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00118 in 1,576,654 control chromosomes in the GnomAD database, including 4 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00092 (1 hom., cov: 0)
  • Exomes 𝑓: 0.0012 (3 hom.)
• Consequence: DDHD1 NM_001160148.2 conservative_inframe_insertion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.972

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 Benign. Variant got -14 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_001160148.2.
• BP6: Variant 14-53152762-T-TGCCGCCGCCGCC is Benign according to our data. Variant chr14-53152762-T-TGCCGCCGCCGCC is described in ClinVar as [Likely_benign]. Clinvar id is 695810.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000923 (139/150676) while in subpopulation NFE AF= 0.00123 (83/67538). AF 95% confidence interval is 0.00102. There are 1 homozygotes in gnomad4. There are 65 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDHD1	NM_001160148.2	c.325_336dupGGCGGCGGCGGC	p.Gly112_Ser113insGlyGlyGlyGly	conservative_inframe_insertion	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.325_336dupGGCGGCGGCGGC	p.Gly112_Ser113insGlyGlyGlyGly	conservative_inframe_insertion	Exon 1 of 13		NM_001160148.2	ENSP00000500986.2
DDHD1	ENST00000357758.3	c.325_336dupGGCGGCGGCGGC	p.Gly112_Ser113insGlyGlyGlyGly	conservative_inframe_insertion	Exon 1 of 12	1		ENSP00000350401.3
DDHD1	ENST00000395606.5	c.325_336dupGGCGGCGGCGGC	p.Gly112_Ser113insGlyGlyGlyGly	conservative_inframe_insertion	Exon 1 of 13	2		ENSP00000378970.1
DDHD1	ENST00000673930.1	c.-159_-148dupGGCGGCGGCGGC		upstream_gene_variant				ENSP00000501087.1

Frequencies

GnomAD3 genomes AF: 0.000923 AC: 139 AN: 150568 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.000757

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000987

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000203

Gnomad SAS AF: 0.000209

Gnomad FIN AF: 0.000191

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00123

Gnomad OTH AF: 0.00241

GnomAD3 exomes AF: 0.000898 AC: 168 AN: 187002 Hom.: 2 AF XY: 0.000793 AC XY: 82 AN XY: 103428

Gnomad AFR exome AF: 0.000288

Gnomad AMR exome AF: 0.00151

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000635

Gnomad SAS exome AF: 0.000424

Gnomad FIN exome AF: 0.000417

Gnomad NFE exome AF: 0.00112

Gnomad OTH exome AF: 0.00167

GnomAD4 exome AF: 0.00121 AC: 1725 AN: 1425978 Hom.: 3 Cov.: 111 AF XY: 0.00116 AC XY: 818 AN XY: 707124

Gnomad4 AFR exome AF: 0.000547

Gnomad4 AMR exome AF: 0.00132

Gnomad4 ASJ exome AF: 0.000120

Gnomad4 EAS exome AF: 0.000442

Gnomad4 SAS exome AF: 0.000361

Gnomad4 FIN exome AF: 0.000285

Gnomad4 NFE exome AF: 0.00138

Gnomad4 OTH exome AF: 0.00115

GnomAD4 genome AF: 0.000923 AC: 139 AN: 150676 Hom.: 1 Cov.: 0 AF XY: 0.000884 AC XY: 65 AN XY: 73548

Gnomad4 AFR AF: 0.000755

Gnomad4 AMR AF: 0.000986

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000203

Gnomad4 SAS AF: 0.000210

Gnomad4 FIN AF: 0.000191

Gnomad4 NFE AF: 0.00123

Gnomad4 OTH AF: 0.00238

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Apr 02, 2020

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hereditary spastic paraplegia 28 Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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;