Variant rs149994413 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 3P and 12B. PM2PP3BP6_Very_StrongBS1

The NM_015214.3(DDHD2):c.558G>A(p.Thr186=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000229 in 1,613,854 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00022 ( 1 hom. )

Consequence

DDHD2
NM_015214.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.27

Variant links:

Genes affected

DDHD2 (HGNC:29106): (DDHD domain containing 2) This gene encodes a phospholipase enzyme containing sterile-alpha-motif (SAM), WWE, and DDHD domains. This protein participates in membrane trafficking between the endoplastic reticulum and the Golgi body. Mutations in this gene can cause autosomal recessive spastic paraplegia 54. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]

DDHD2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

BP6

Variant 8-38238145-G-A is Benign according to our data. Variant chr8-38238145-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 385430.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.000224 (328/1461632) while in subpopulation AMR AF= 0.000784 (35/44666). AF 95% confidence interval is 0.000578. There are 1 homozygotes in gnomad4_exome. There are 160 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDHD2	NM_015214.3 linkuse as main transcript	c.558G>A	p.Thr186=	synonymous_variant	5/18	ENST00000397166.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDHD2	ENST00000397166.7 linkuse as main transcript	c.558G>A	p.Thr186=	synonymous_variant	5/18	2	NM_015214.3	P1	O94830-1

Frequencies

GnomAD3 genomes

AF:

0.000276

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00547

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000482

AC:

121

AN:

251088

Hom.:

AF XY:

0.000391

AC XY:

AN XY:

135690

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000667

Gnomad ASJ exome

AF:

0.00665

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000203

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.000224

AC:

328

AN:

1461632

Hom.:

Cov.:

AF XY:

0.000220

AC XY:

160

AN XY:

727110

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000784

Gnomad4 ASJ exome

AF:

0.00639

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000881

Gnomad4 OTH exome

AF:

0.000447

GnomAD4 genome

AF:

0.000276

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.000229

AC XY:

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.000393

Gnomad4 ASJ

AF:

0.00547

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000691

Hom.:

Bravo

AF:

0.000321

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000356

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Oct 20, 2020

- -

Hereditary spastic paraplegia 54

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 19, 2024

- -

Hereditary spastic paraplegia

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Jul 01, 2020

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

May 03, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

DANN

Benign

0.53

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.56

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.56

Position offset: 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