chr8-38234508-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP6_ModerateBS1

The NM_015214.3(DDHD2):​c.335G>A​(p.Arg112Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000273 in 1,613,146 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

DDHD2
NM_015214.3 missense

Scores

10
5
4

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 9.36
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP6
Variant 8-38234508-G-A is Benign according to our data. Variant chr8-38234508-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 540291.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.0000274 (40/1460986) while in subpopulation EAS AF= 0.000833 (33/39614). AF 95% confidence interval is 0.000609. There are 0 homozygotes in gnomad4_exome. There are 24 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DDHD2NM_015214.3 linkuse as main transcriptc.335G>A p.Arg112Gln missense_variant 3/18 ENST00000397166.7 NP_056029.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DDHD2ENST00000397166.7 linkuse as main transcriptc.335G>A p.Arg112Gln missense_variant 3/182 NM_015214.3 ENSP00000380352 P1O94830-1

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152160
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000770
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000212
AC:
53
AN:
250398
Hom.:
0
AF XY:
0.000192
AC XY:
26
AN XY:
135420
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00284
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000880
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000274
AC:
40
AN:
1460986
Hom.:
0
Cov.:
31
AF XY:
0.0000330
AC XY:
24
AN XY:
726834
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000833
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000450
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152160
Hom.:
0
Cov.:
32
AF XY:
0.0000404
AC XY:
3
AN XY:
74340
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000770
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000422
Hom.:
0
Bravo
AF:
0.0000869
ExAC
AF:
0.000157
AC:
19

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Hereditary spastic paraplegia 54 Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpOct 05, 2022- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.75
BayesDel_addAF
Benign
-0.021
T
BayesDel_noAF
Pathogenic
0.19
CADD
Pathogenic
30
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.41
T;T;T;T;.;.;T
Eigen
Pathogenic
1.0
Eigen_PC
Pathogenic
0.97
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.97
D;.;D;D;D;D;D
M_CAP
Benign
0.048
D
MetaRNN
Uncertain
0.59
D;D;D;D;D;D;D
MetaSVM
Uncertain
-0.24
T
MutationAssessor
Pathogenic
3.1
.;M;.;.;.;.;M
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.71
T
PROVEAN
Uncertain
-4.0
D;D;D;D;D;D;D
REVEL
Pathogenic
0.75
Sift
Pathogenic
0.0
D;D;D;D;D;D;D
Sift4G
Pathogenic
0.0
D;D;D;D;D;D;D
Polyphen
1.0
.;D;.;.;.;D;D
Vest4
0.96
MutPred
0.94
Loss of MoRF binding (P = 0.0417);Loss of MoRF binding (P = 0.0417);Loss of MoRF binding (P = 0.0417);.;.;Loss of MoRF binding (P = 0.0417);Loss of MoRF binding (P = 0.0417);
MVP
0.67
MPC
0.63
ClinPred
0.31
T
GERP RS
5.8
Varity_R
0.74
gMVP
0.88

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.11
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.

Other links and lift over

dbSNP: rs781089161; hg19: chr8-38092026; API