14-53152366-C-T

Position:

chr14-53152366-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001160148.2(DDHD1):c.733G>A(p.Glu245Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000192 in 1,613,818 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0010 ( 3 hom., cov: 33)

Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

DDHD1
NM_001160148.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.43

Variant links:

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 links:

DDHD1 (HGNC:):

DDHD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0068194866).

BP6

Variant 14-53152366-C-T is Benign according to our data. Variant chr14-53152366-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 695663.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00103 (157/152328) while in subpopulation AFR AF= 0.00368 (153/41588). AF 95% confidence interval is 0.0032. There are 3 homozygotes in gnomad4. There are 69 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDHD1	NM_001160148.2 linkuse as main transcript	c.733G>A	p.Glu245Lys	missense_variant	1/13	ENST00000673822.2	NP_001153620.1	Q8NEL9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDHD1	ENST00000673822.2 linkuse as main transcript	c.733G>A	p.Glu245Lys	missense_variant	1/13		NM_001160148.2	ENSP00000500986.2		Q8NEL9-1

Frequencies

GnomAD3 genomes

AF:

0.00104

AC:

158

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00371

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000216

AC:

AN:

250066

Hom.:

AF XY:

0.000177

AC XY:

AN XY:

135544

show subpopulations

Gnomad AFR exome

AF:

0.00318

Gnomad AMR exome

AF:

0.0000580

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000105

AC:

153

AN:

1461490

Hom.:

Cov.:

AF XY:

0.0000963

AC XY:

AN XY:

727090

show subpopulations

Gnomad4 AFR exome

AF:

0.00412

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.000133

GnomAD4 genome

AF:

0.00103

AC:

157

AN:

152328

Hom.:

Cov.:

AF XY:

0.000926

AC XY:

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.00368

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000292

Hom.:

Bravo

AF:

0.00111

ESP6500AA

AF:

0.00363

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000264

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Hereditary spastic paraplegia 28

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 19, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

DANN

Benign

0.93

DEOGEN2

Benign

0.0062

.;T;.

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.36

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.82

T;T;T

M_CAP

Benign

0.033

MetaRNN

Benign

0.0068

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

2.0

M;M;M

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.53

N;N;N

REVEL

Benign

0.057

Sift

Benign

0.38

T;T;T

Sift4G

Benign

0.79

T;T;T

Polyphen

0.13, 0.13

.;B;B

Vest4

0.33

MVP

0.082

MPC

0.52

ClinPred

0.020

GERP RS

3.2

Varity_R

0.15

gMVP

0.32

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over