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rs202097155

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_145038.5(DRC1):c.2021A>T(p.Gln674Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000874 in 1,614,194 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0012 ( 3 hom., cov: 32)
Exomes 𝑓: 0.00084 ( 3 hom. )

Consequence

DRC1
NM_145038.5 missense

Scores

19

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.204
Variant links:
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 Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0049669743).
BP6
Variant 2-26454748-A-T is Benign according to our data. Variant chr2-26454748-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 414284.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00116 (176/152306) while in subpopulation NFE AF= 0.00163 (111/68012). AF 95% confidence interval is 0.00139. There are 3 homozygotes in gnomad4. There are 97 alleles in male gnomad4 subpopulation. This position pass quality control queck.
BS2
High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
DRC1NM_145038.5 linkuse as main transcriptc.2021A>T p.Gln674Leu missense_variant 15/17 ENST00000288710.7
DRC1XM_047446339.1 linkuse as main transcriptc.1001A>T p.Gln334Leu missense_variant 8/10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
DRC1ENST00000288710.7 linkuse as main transcriptc.2021A>T p.Gln674Leu missense_variant 15/172 NM_145038.5 P1
DRC1ENST00000649059.1 linkuse as main transcriptc.*984A>T 3_prime_UTR_variant, NMD_transcript_variant 14/16

Frequencies

GnomAD3 genomes
AF:
0.00116
AC:
176
AN:
152188
Hom.:
3
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00403
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00452
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00163
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.00110
AC:
276
AN:
251438
Hom.:
1
AF XY:
0.00107
AC XY:
146
AN XY:
135900
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00288
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00388
Gnomad NFE exome
AF:
0.00140
Gnomad OTH exome
AF:
0.000653
GnomAD4 exome
AF:
0.000844
AC:
1234
AN:
1461888
Hom.:
3
Cov.:
31
AF XY:
0.000866
AC XY:
630
AN XY:
727246
show subpopulations
Gnomad4 AFR exome
AF:
0.000119
Gnomad4 AMR exome
AF:
0.0000671
Gnomad4 ASJ exome
AF:
0.00310
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00474
Gnomad4 NFE exome
AF:
0.000754
Gnomad4 OTH exome
AF:
0.000861
GnomAD4 genome
AF:
0.00116
AC:
176
AN:
152306
Hom.:
3
Cov.:
32
AF XY:
0.00130
AC XY:
97
AN XY:
74466
show subpopulations
Gnomad4 AFR
AF:
0.0000481
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00403
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00452
Gnomad4 NFE
AF:
0.00163
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.00156
Hom.:
2
Bravo
AF:
0.000548
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.000778
AC:
3
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000698
AC:
6
ExAC
AF:
0.00133
AC:
161
EpiCase
AF:
0.00136
EpiControl
AF:
0.00101

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Primary ciliary dyskinesia Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeJan 18, 2024- -
DRC1-related disorder Benign:1
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesFeb 17, 2022This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.081
BayesDel_addAF
Benign
-0.54
T
BayesDel_noAF
Benign
-0.55
Cadd
Benign
0.24
Dann
Benign
0.66
DEOGEN2
Benign
0.00083
T
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.056
N
LIST_S2
Benign
0.54
T
M_CAP
Benign
0.0052
T
MetaRNN
Benign
0.0050
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.35
N
MutationTaster
Benign
0.66
D
PrimateAI
Benign
0.29
T
PROVEAN
Benign
-0.51
N
REVEL
Benign
0.031
Sift
Benign
0.73
T
Sift4G
Benign
0.70
T
Polyphen
0.0
B
Vest4
0.16
MVP
0.12
MPC
0.055
ClinPred
0.013
T
GERP RS
-0.66
Varity_R
0.093
gMVP
0.23

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.

Other links and lift over

dbSNP: rs202097155; hg19: chr2-26677616; API