14-53046759-CAA-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001160148.2(DDHD1):c.*7_*8del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00773 in 1,214,006 control chromosomes in the GnomAD database, including 491 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (251 hom., cov: 0)
  • Exomes 𝑓: 0.0039 (240 hom.)
• Consequence: DDHD1 NM_001160148.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.414

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 -10 ACMG points.

• BP6: Variant 14-53046759-CAA-C is Benign according to our data. Variant chr14-53046759-CAA-C is described in ClinVar as [Benign]. Clinvar id is 1182240.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDHD1	NM_001160148.2	c.*7_*8del		3_prime_UTR_variant	13/13	ENST00000673822.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDHD1	ENST00000673822.2	c.*7_*8del		3_prime_UTR_variant	13/13		NM_001160148.2	A2

Frequencies

GnomAD3 genomes AF: 0.105 AC: 4770 AN: 45280 Hom.: 251 Cov.: 0

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0702

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0152

Gnomad SAS AF: 0.00210

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0490

Gnomad NFE AF: 0.00153

Gnomad OTH AF: 0.0757

GnomAD3 exomes AF: 0.0340 AC: 1775 AN: 52278 Hom.: 103 AF XY: 0.0232 AC XY: 668 AN XY: 28740

Gnomad AFR exome AF: 0.276

Gnomad AMR exome AF: 0.0390

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0194

Gnomad SAS exome AF: 0.000410

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00167

Gnomad OTH exome AF: 0.0248

GnomAD4 exome AF: 0.00395 AC: 4613 AN: 1168714 Hom.: 240 AF XY: 0.00358 AC XY: 2083 AN XY: 581178

Gnomad4 AFR exome AF: 0.128

Gnomad4 AMR exome AF: 0.0103

Gnomad4 ASJ exome AF: 0.0000477

Gnomad4 EAS exome AF: 0.000145

Gnomad4 SAS exome AF: 0.000301

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000485

Gnomad4 OTH exome AF: 0.00867

GnomAD4 genome AF: 0.105 AC: 4772 AN: 45292 Hom.: 251 Cov.: 0 AF XY: 0.105 AC XY: 2245 AN XY: 21456

Gnomad4 AFR AF: 0.274

Gnomad4 AMR AF: 0.0702

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0153

Gnomad4 SAS AF: 0.00212

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00153

Gnomad4 OTH AF: 0.0747

Alfa AF: 0.0239 Hom.: 9

Bravo AF: 0.0364

Asia WGS AF: 0.0100 AC: 19 AN: 1804

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 21, 2017

- -

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: rs33960665; hg19: chr14-53513477;