Variant 2-26444262-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_145038.5(DRC1):c.1069A>G(p.Lys357Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 1,614,000 control chromosomes in the GnomAD database, including 24,958 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 2080 hom., cov: 32)

Exomes 𝑓: 0.17 ( 22878 hom. )

Consequence

DRC1
NM_145038.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 2.89

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0059809983).

BP6

Variant 2-26444262-A-G is Benign according to our data. Variant chr2-26444262-A-G is described in ClinVar as [Benign]. Clinvar id is 402796.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DRC1	NM_145038.5 linkuse as main transcript	c.1069A>G	p.Lys357Glu	missense_variant	9/17	ENST00000288710.7	NP_659475.2
DRC1	XM_047446339.1 linkuse as main transcript	c.49A>G	p.Lys17Glu	missense_variant	2/10		XP_047302295.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DRC1	ENST00000288710.7 linkuse as main transcript	c.1069A>G	p.Lys357Glu	missense_variant	9/17	2	NM_145038.5	ENSP00000288710	P1

Frequencies

GnomAD3 genomes

AF:

0.146

AC:

22187

AN:

152098

Hom.:

2074

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0326

Gnomad AMI

AF:

0.262

Gnomad AMR

AF:

0.175

Gnomad ASJ

AF:

0.217

Gnomad EAS

AF:

0.217

Gnomad SAS

AF:

0.212

Gnomad FIN

AF:

0.263

Gnomad MID

AF:

0.187

Gnomad NFE

AF:

0.174

Gnomad OTH

AF:

0.166

GnomAD3 exomes

AF:

0.190

AC:

47660

AN:

251296

Hom.:

5031

AF XY:

0.190

AC XY:

25791

AN XY:

135832

show subpopulations

Gnomad AFR exome

AF:

0.0277

Gnomad AMR exome

AF:

0.235

Gnomad ASJ exome

AF:

0.215

Gnomad EAS exome

AF:

0.225

Gnomad SAS exome

AF:

0.202

Gnomad FIN exome

AF:

0.259

Gnomad NFE exome

AF:

0.174

Gnomad OTH exome

AF:

0.195

GnomAD4 exome

AF:

0.172

AC:

251588

AN:

1461786

Hom.:

22878

Cov.:

AF XY:

0.173

AC XY:

125674

AN XY:

727192

show subpopulations

Gnomad4 AFR exome

AF:

0.0259

Gnomad4 AMR exome

AF:

0.228

Gnomad4 ASJ exome

AF:

0.215

Gnomad4 EAS exome

AF:

0.195

Gnomad4 SAS exome

AF:

0.197

Gnomad4 FIN exome

AF:

0.254

Gnomad4 NFE exome

AF:

0.166

Gnomad4 OTH exome

AF:

0.175

GnomAD4 genome

AF:

0.146

AC:

22195

AN:

152214

Hom.:

2080

Cov.:

AF XY:

0.152

AC XY:

11298

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.0325

Gnomad4 AMR

AF:

0.175

Gnomad4 ASJ

AF:

0.217

Gnomad4 EAS

AF:

0.217

Gnomad4 SAS

AF:

0.212

Gnomad4 FIN

AF:

0.263

Gnomad4 NFE

AF:

0.174

Gnomad4 OTH

AF:

0.171

Alfa

AF:

0.170

Hom.:

5676

Bravo

AF:

0.135

TwinsUK

AF:

0.152

AC:

565

ALSPAC

AF:

0.153

AC:

589

ESP6500AA

AF:

0.0354

AC:

156

ESP6500EA

AF:

0.171

AC:

1473

ExAC

AF:

0.184

AC:

22338

Asia WGS

AF:

0.269

AC:

933

AN:

3478

EpiCase

AF:

0.176

EpiControl

AF:

0.175

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Primary ciliary dyskinesia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Primary ciliary dyskinesia 21

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0089

Eigen

Uncertain

0.19

Eigen_PC

Benign

0.20

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.67

MetaRNN

Benign

0.0060

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.8

MutationTaster

Benign

0.53

PrimateAI

Benign

0.42

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.059

Sift

Uncertain

0.0040

Sift4G

Benign

0.14

Polyphen

0.92

Vest4

0.34

MPC

0.26

ClinPred

0.025

GERP RS

4.2

Varity_R

0.30

gMVP

0.10

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