Variant rs202097155 details in Genebe, Genetics Data Aggregator

Variant summary

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

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

Clinical Significance

Likely benign criteria provided, single submitter 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]

DRC1 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=0.0049669743).

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_single_submitter, 1 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. Median coverage is 32. 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
DRC1	NM_145038.5 linkuse as main transcript	c.2021A>T	p.Gln674Leu	missense_variant	15/17	ENST00000288710.7	NP_659475.2
DRC1	XM_047446339.1 linkuse as main transcript	c.1001A>T	p.Gln334Leu	missense_variant	8/10		XP_047302295.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DRC1	ENST00000288710.7 linkuse as main transcript	c.2021A>T	p.Gln674Leu	missense_variant	15/17	2	NM_145038.5	ENSP00000288710	P1
DRC1	ENST00000649059.1 linkuse as main transcript	c.*984A>T		3_prime_UTR_variant, NMD_transcript_variant	14/16			ENSP00000497543

Frequencies

GnomAD3 genomes

AF:

0.00116

AC:

176

AN:

152188

Hom.:

Cov.:

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.:

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.:

Cov.:

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.:

Cov.:

AF XY:

0.00130

AC XY:

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.:

Bravo

AF:

0.000548

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000698

AC:

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, single submitter

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 18, 2024

- -

DRC1-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 17, 2022

This 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

BayesDel_noAF

Benign

-0.55

CADD

Benign

0.24

DANN

Benign

0.66

DEOGEN2

Benign

0.00083

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.056

LIST_S2

Benign

0.54

M_CAP

Benign

0.0052

MetaRNN

Benign

0.0050

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.35

MutationTaster

Benign

0.66

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.51

REVEL

Benign

0.031

Sift

Benign

0.73

Sift4G

Benign

0.70

Polyphen

0.0

Vest4

0.16

MVP

0.12

MPC

0.055

ClinPred

0.013

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.

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