rs574881831
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_145038.5(DRC1):c.463G>A(p.Glu155Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000204 in 1,613,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000021 ( 0 hom. )
Consequence
DRC1
NM_145038.5 missense
NM_145038.5 missense
Scores
7
12
Clinical Significance
Conservation
PhyloP100: 3.72
Genes affected
DRC1 (HGNC:24245): (dynein regulatory complex subunit 1) This gene encodes a central component of the nexin-dynein complex (N-DRC), which regulates the assembly of ciliary dynein. Mutations in this gene can cause ciliary dyskinesia. [provided by RefSeq, Aug 2015]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.023224741).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DRC1 | NM_145038.5 | c.463G>A | p.Glu155Lys | missense_variant | 4/17 | ENST00000288710.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DRC1 | ENST00000288710.7 | c.463G>A | p.Glu155Lys | missense_variant | 4/17 | 2 | NM_145038.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000198 AC: 3AN: 151882Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.000119 AC: 30AN: 251248Hom.: 0 AF XY: 0.0000884 AC XY: 12AN XY: 135780
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GnomAD4 exome AF: 0.0000205 AC: 30AN: 1461868Hom.: 0 Cov.: 30 AF XY: 0.0000165 AC XY: 12AN XY: 727234
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152000Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74288
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 11, 2023 | The c.463G>A (p.E155K) alteration is located in exon 4 (coding exon 4) of the DRC1 gene. This alteration results from a G to A substitution at nucleotide position 463, causing the glutamic acid (E) at amino acid position 155 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Primary ciliary dyskinesia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 05, 2022 | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 155 of the DRC1 protein (p.Glu155Lys). This variant is present in population databases (rs574881831, gnomAD 0.2%). This variant has not been reported in the literature in individuals affected with DRC1-related conditions. ClinVar contains an entry for this variant (Variation ID: 525381). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
D
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Uncertain
T
Polyphen
P
Vest4
MutPred
Gain of MoRF binding (P = 0.0037);
MVP
MPC
ClinPred
T
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at