NM_145038.5:c.2200G>A

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.2200G>A(p.Val734Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0536 in 1,614,084 control chromosomes in the GnomAD database, including 2,640 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. V734V) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.042 ( 182 hom., cov: 33)

Exomes 𝑓: 0.055 ( 2458 hom. )

Consequence

DRC1
NM_145038.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 2.19

Publications

13 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=0.0021615028).

BP6

Variant 2-26456494-G-A is Benign according to our data. Variant chr2-26456494-G-A is described in ClinVar as Benign. ClinVar VariationId is 402799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0604 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRC1	NM_145038.5 link	c.2200G>A	p.Val734Met	missense_variant	Exon 17 of 17	ENST00000288710.7	NP_659475.2	Q96MC2
DRC1	XM_047446339.1 link	c.1180G>A	p.Val394Met	missense_variant	Exon 10 of 10		XP_047302295.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DRC1	ENST00000288710.7 link	c.2200G>A	p.Val734Met	missense_variant	Exon 17 of 17	2	NM_145038.5	ENSP00000288710.2	Q96MC2
DRC1	ENST00000649059.1 link	n.*1163G>A		non_coding_transcript_exon_variant	Exon 16 of 16			ENSP00000497543.1	A0A3B3IT12
DRC1	ENST00000649059.1 link	n.*1163G>A		3_prime_UTR_variant	Exon 16 of 16			ENSP00000497543.1	A0A3B3IT12

Frequencies

GnomAD3 genomes

AF:

0.0419

AC:

6378

AN:

152190

Hom.:

182

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0116

Gnomad AMI

AF:

0.0549

Gnomad AMR

AF:

0.0561

Gnomad ASJ

AF:

0.0881

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0217

Gnomad FIN

AF:

0.0210

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0619

Gnomad OTH

AF:

0.0607

GnomAD2 exomes

AF:

0.0411

AC:

10326

AN:

251352

AF XY:

0.0423

show subpopulations

Gnomad AFR exome

AF:

0.00886

Gnomad AMR exome

AF:

0.0279

Gnomad ASJ exome

AF:

0.0910

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.0219

Gnomad NFE exome

AF:

0.0600

Gnomad OTH exome

AF:

0.0521

GnomAD4 exome

AF:

0.0548

AC:

80152

AN:

1461776

Hom.:

2458

Cov.:

AF XY:

0.0541

AC XY:

39305

AN XY:

727196

show subpopulations

African (AFR)

AF:

0.00929

AC:

311

AN:

33480

American (AMR)

AF:

0.0300

AC:

1339

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.0894

AC:

2336

AN:

26132

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39700

South Asian (SAS)

AF:

0.0226

AC:

1949

AN:

86246

European-Finnish (FIN)

AF:

0.0224

AC:

1198

AN:

53418

Middle Eastern (MID)

AF:

0.0562

AC:

324

AN:

5764

European-Non Finnish (NFE)

AF:

0.0625

AC:

69475

AN:

1111940

Other (OTH)

AF:

0.0533

AC:

3217

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

4108

8216

12324

16432

20540

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2522

5044

7566

10088

12610

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0418

AC:

6374

AN:

152308

Hom.:

182

Cov.:

AF XY:

0.0395

AC XY:

2943

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.0116

AC:

481

AN:

41566

American (AMR)

AF:

0.0560

AC:

857

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0881

AC:

306

AN:

3472

East Asian (EAS)

AF:

0.000386

AC:

AN:

5184

South Asian (SAS)

AF:

0.0213

AC:

103

AN:

4828

European-Finnish (FIN)

AF:

0.0210

AC:

223

AN:

10614

Middle Eastern (MID)

AF:

0.0442

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0619

AC:

4212

AN:

68018

Other (OTH)

AF:

0.0601

AC:

127

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

328

656

985

1313

1641

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

216

288

360

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0546

Hom.:

568

Bravo

AF:

0.0437

TwinsUK

AF:

0.0663

AC:

246

ALSPAC

AF:

0.0542

AC:

209

ESP6500AA

AF:

0.00931

AC:

ESP6500EA

AF:

0.0640

AC:

550

ExAC

AF:

0.0406

AC:

4929

Asia WGS

AF:

0.0110

AC:

AN:

3478

EpiCase

AF:

0.0638

EpiControl

AF:

0.0628

ClinVar

Significance: Benign

Submissions summary: Benign:4

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0019

Eigen

Benign

-0.094

Eigen_PC

Benign

0.024

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.74

MetaRNN

Benign

0.0022

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.0

PhyloP100

2.2

PrimateAI

Benign

0.48

PROVEAN

Benign

-0.94

REVEL

Benign

0.070

Sift

Benign

0.18

Sift4G

Benign

0.19

Polyphen

0.063

Vest4

0.090

MPC

0.15

ClinPred

0.024

GERP RS

4.8

Varity_R

0.082

gMVP

0.19

Mutation Taster

=99/1

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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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