14-53046752-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001160148.2(DDHD1):c.*16A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00122 in 1,436,872 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.022 (10 hom., cov: 30)
  • Exomes 𝑓: 0.00060 (11 hom.)
• Consequence: DDHD1 NM_001160148.2 3_prime_UTR
• Clinical Significance: Likely 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 14-53046752-T-C is Benign according to our data. Variant chr14-53046752-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 382967.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.075 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDHD1	NM_001160148.2	c.*16A>G		3_prime_UTR_variant	13/13	ENST00000673822.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDHD1	ENST00000673822.2	c.*16A>G		3_prime_UTR_variant	13/13		NM_001160148.2	A2

Frequencies

GnomAD3 genomes AF: 0.0217 AC: 907 AN: 41842 Hom.: 10 Cov.: 30

Gnomad AFR AF: 0.0793

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00650

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00194

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000928

Gnomad OTH AF: 0.0137

GnomAD3 exomes AF: 0.00386 AC: 332 AN: 85992 Hom.: 2 AF XY: 0.00255 AC XY: 120 AN XY: 47112

Gnomad AFR exome AF: 0.0510

Gnomad AMR exome AF: 0.00279

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000332

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000607

GnomAD4 exome AF: 0.000601 AC: 838 AN: 1395030 Hom.: 11 Cov.: 25 AF XY: 0.000489 AC XY: 339 AN XY: 692598

Gnomad4 AFR exome AF: 0.0233

Gnomad4 AMR exome AF: 0.000806

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000930

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000186

Gnomad4 OTH exome AF: 0.00129

GnomAD4 genome AF: 0.0217 AC: 909 AN: 41842 Hom.: 10 Cov.: 30 AF XY: 0.0216 AC XY: 430 AN XY: 19920

Gnomad4 AFR AF: 0.0793

Gnomad4 AMR AF: 0.00650

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00196

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000928

Gnomad4 OTH AF: 0.0135

Alfa AF: 0.000903 Hom.: 0

Bravo AF: 0.00666

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

Jan 02, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
Cadd	Benign	10
Dann	Benign	0.66

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: rs112663760; hg19: chr14-53513470;