14-53046607-ACTT-A

Variant names:

• chr14-53046607-ACTT-A
• rs142139070
• ENST00000556027.5:n.3368_3370delAAG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001160148.2(DDHD1):​c.*158_*160delAAG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0365 in 467,758 control chromosomes in the GnomAD database, including 1,201 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.072 (998 hom., cov: 31)
  • Exomes 𝑓: 0.020 (203 hom.)
• Consequence: DDHD1 NM_001160148.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.132
• Publications: 1 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 Gene-Disease associations (from GenCC):

• hereditary spastic paraplegia

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• hereditary spastic paraplegia 28

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 14-53046607-ACTT-A is Benign according to our data. Variant chr14-53046607-ACTT-A is described in ClinVar as [Benign]. Clinvar id is 1183899.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDHD1	NM_001160148.2	c.*158_*160delAAG		3_prime_UTR_variant	Exon 13 of 13	ENST00000673822.2	NP_001153620.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDHD1	ENST00000673822.2	c.*158_*160delAAG		3_prime_UTR_variant	Exon 13 of 13		NM_001160148.2	ENSP00000500986.2

Frequencies

GnomAD3 genomes AF: 0.0718 AC: 10893 AN: 151722 Hom.: 997 Cov.: 31

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.0387

Gnomad ASJ AF: 0.0337

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00685

Gnomad FIN AF: 0.00370

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0147

Gnomad OTH AF: 0.0579

GnomAD4 exome AF: 0.0195 AC: 6176 AN: 315916 Hom.: 203 AF XY: 0.0185 AC XY: 2981 AN XY: 161482

African (AFR) AF: 0.210 AC: 1649 AN: 7840

American (AMR) AF: 0.0284 AC: 234 AN: 8252

Ashkenazi Jewish (ASJ) AF: 0.0400 AC: 392 AN: 9808

East Asian (EAS) AF: 0.0000871 AC: 2 AN: 22960

South Asian (SAS) AF: 0.00703 AC: 73 AN: 10378

European-Finnish (FIN) AF: 0.00304 AC: 102 AN: 33498

Middle Eastern (MID) AF: 0.0325 AC: 47 AN: 1446

European-Non Finnish (NFE) AF: 0.0151 AC: 3078 AN: 203326

Other (OTH) AF: 0.0325 AC: 599 AN: 18408

GnomAD4 genome AF: 0.0719 AC: 10910 AN: 151842 Hom.: 998 Cov.: 31 AF XY: 0.0696 AC XY: 5162 AN XY: 74192

African (AFR) AF: 0.215 AC: 8901 AN: 41320

American (AMR) AF: 0.0385 AC: 586 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.0337 AC: 117 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5194

South Asian (SAS) AF: 0.00686 AC: 33 AN: 4812

European-Finnish (FIN) AF: 0.00370 AC: 39 AN: 10550

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0147 AC: 997 AN: 67954

Other (OTH) AF: 0.0568 AC: 120 AN: 2112

Alfa AF: 0.0494 Hom.: 56

Bravo AF: 0.0806

Asia WGS AF: 0.0150 AC: 52 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 31, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.13
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs142139070; hg19: chr14-53513325;