NM_145038.5:c.1069A>G

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

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

Publications

27 publications found

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 Gene-Disease associations (from GenCC):

primary ciliary dyskinesia 21
Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae)
primary ciliary dyskinesia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
spermatogenic failure 80
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

DRC1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
DRC1	NM_145038.5 link	c.1069A>G	p.Lys357Glu	missense_variant	Exon 9 of 17	ENST00000288710.7	NP_659475.2	Q96MC2
DRC1	XM_047446339.1 link	c.49A>G	p.Lys17Glu	missense_variant	Exon 2 of 10		XP_047302295.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DRC1	ENST00000288710.7 link	c.1069A>G	p.Lys357Glu	missense_variant	Exon 9 of 17	2	NM_145038.5	ENSP00000288710.2		Q96MC2

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

GnomAD2 exomes

AF:

0.190

AC:

47660

AN:

251296

AF XY:

0.190

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 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

African (AFR)

AF:

0.0259

AC:

866

AN:

33478

American (AMR)

AF:

0.228

AC:

10206

AN:

44692

Ashkenazi Jewish (ASJ)

AF:

0.215

AC:

5618

AN:

26132

East Asian (EAS)

AF:

0.195

AC:

7751

AN:

39700

South Asian (SAS)

AF:

0.197

AC:

16957

AN:

86248

European-Finnish (FIN)

AF:

0.254

AC:

13565

AN:

53386

Middle Eastern (MID)

AF:

0.163

AC:

942

AN:

5768

European-Non Finnish (NFE)

AF:

0.166

AC:

185101

AN:

1111986

Other (OTH)

AF:

0.175

AC:

10582

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

11933

23866

35799

47732

59665

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.146

AC:

22195

AN:

152214

Hom.:

2080

Cov.:

AF XY:

0.152

AC XY:

11298

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.0325

AC:

1349

AN:

41562

American (AMR)

AF:

0.175

AC:

2671

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.217

AC:

753

AN:

3472

East Asian (EAS)

AF:

0.217

AC:

1122

AN:

5180

South Asian (SAS)

AF:

0.212

AC:

1020

AN:

4820

European-Finnish (FIN)

AF:

0.263

AC:

2783

AN:

10568

Middle Eastern (MID)

AF:

0.177

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.174

AC:

11846

AN:

68014

Other (OTH)

AF:

0.171

AC:

361

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

944

1888

2833

3777

4721

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.166

Hom.:

10033

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

Jul 09, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Primary ciliary dyskinesia 21

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

(source)

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

PhyloP100

2.9

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

Mutation Taster

=89/11

polymorphism (auto)

(source)

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

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NM_145038.5:c.1069A>G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over