14-53046611-C-CT

Position:

• chr14-53046611-C-CT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001160148.2(DDHD1):​c.*156_*157insA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00524 in 413,008 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0047 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0055 (0 hom.)
• Consequence: DDHD1 NM_001160148.2 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.71

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 14-53046611-C-CT is Benign according to our data. Variant chr14-53046611-C-CT is described in ClinVar as [Likely_benign]. Clinvar id is 1218404.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00468 (604/128970) while in subpopulation AFR AF= 0.018 (454/25170). AF 95% confidence interval is 0.0167. There are 2 homozygotes in gnomad4. There are 308 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDHD1	NM_001160148.2	c.*156_*157insA		3_prime_UTR_variant	13/13	ENST00000673822.2	NP_001153620.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDHD1	ENST00000673822.2	c.*156_*157insA		3_prime_UTR_variant	13/13		NM_001160148.2	ENSP00000500986	A2

Frequencies

GnomAD3 genomes AF: 0.00467 AC: 602 AN: 128906 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.0180

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00661

Gnomad ASJ AF: 0.000627

Gnomad EAS AF: 0.000782

Gnomad SAS AF: 0.000434

Gnomad FIN AF: 0.000104

Gnomad MID AF: 0.00350

Gnomad NFE AF: 0.000648

Gnomad OTH AF: 0.00442

GnomAD4 exome AF: 0.00550 AC: 1561 AN: 284038 Hom.: 0 Cov.: 5 AF XY: 0.00567 AC XY: 822 AN XY: 144898

Gnomad4 AFR exome AF: 0.0188

Gnomad4 AMR exome AF: 0.00903

Gnomad4 ASJ exome AF: 0.00475

Gnomad4 EAS exome AF: 0.00361

Gnomad4 SAS exome AF: 0.00773

Gnomad4 FIN exome AF: 0.00380

Gnomad4 NFE exome AF: 0.00546

Gnomad4 OTH exome AF: 0.00425

GnomAD4 genome AF: 0.00468 AC: 604 AN: 128970 Hom.: 2 Cov.: 32 AF XY: 0.00488 AC XY: 308 AN XY: 63134

Gnomad4 AFR AF: 0.0180

Gnomad4 AMR AF: 0.00660

Gnomad4 ASJ AF: 0.000627

Gnomad4 EAS AF: 0.000785

Gnomad4 SAS AF: 0.000435

Gnomad4 FIN AF: 0.000104

Gnomad4 NFE AF: 0.000648

Gnomad4 OTH AF: 0.00438

Bravo AF: 0.00453

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 02, 2019

- -

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: rs113463836; hg19: chr14-53513329;