2-26424409-T-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_145038.5(DRC1):c.495T>G(p.Ala165Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.842 in 1,613,406 control chromosomes in the GnomAD database, including 585,512 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. A165A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.76 ( 46068 hom., cov: 29)

Exomes 𝑓: 0.85 ( 539444 hom. )

Consequence

DRC1
NM_145038.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -2.06

Publications

17 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 2-26424409-T-G is Benign according to our data. Variant chr2-26424409-T-G is described in ClinVar as Benign. ClinVar VariationId is 262566.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.06 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.884 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145038.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRC1	NM_145038.5	MANE Select	c.495T>G	p.Ala165Ala	synonymous	Exon 4 of 17	NP_659475.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DRC1	ENST00000288710.7	TSL:2 MANE Select	c.495T>G	p.Ala165Ala	synonymous	Exon 4 of 17	ENSP00000288710.2
DRC1	ENST00000421869.5	TSL:1	n.356+3009T>G		intron	N/A	ENSP00000414375.1
DRC1	ENST00000497651.1	TSL:5	n.385T>G		non_coding_transcript_exon	Exon 2 of 4

Frequencies

GnomAD3 genomes

AF:

0.760

AC:

115199

AN:

151614

Hom.:

46066

Cov.:

show subpopulations

Gnomad AFR

AF:

0.567

Gnomad AMI

AF:

0.906

Gnomad AMR

AF:

0.695

Gnomad ASJ

AF:

0.859

Gnomad EAS

AF:

0.309

Gnomad SAS

AF:

0.771

Gnomad FIN

AF:

0.929

Gnomad MID

AF:

0.816

Gnomad NFE

AF:

0.890

Gnomad OTH

AF:

0.781

GnomAD2 exomes

AF:

0.774

AC:

194160

AN:

250974

AF XY:

0.790

show subpopulations

Gnomad AFR exome

AF:

0.554

Gnomad AMR exome

AF:

0.600

Gnomad ASJ exome

AF:

0.858

Gnomad EAS exome

AF:

0.305

Gnomad FIN exome

AF:

0.929

Gnomad NFE exome

AF:

0.892

Gnomad OTH exome

AF:

0.826

GnomAD4 exome

AF:

0.850

AC:

1243105

AN:

1461676

Hom.:

539444

Cov.:

AF XY:

0.851

AC XY:

618458

AN XY:

727130

show subpopulations

African (AFR)

AF:

0.555

AC:

18586

AN:

33474

American (AMR)

AF:

0.614

AC:

27473

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.852

AC:

22257

AN:

26136

East Asian (EAS)

AF:

0.306

AC:

12160

AN:

39696

South Asian (SAS)

AF:

0.780

AC:

67294

AN:

86238

European-Finnish (FIN)

AF:

0.926

AC:

49454

AN:

53408

Middle Eastern (MID)

AF:

0.801

AC:

4520

AN:

5642

European-Non Finnish (NFE)

AF:

0.892

AC:

991707

AN:

1111986

Other (OTH)

AF:

0.822

AC:

49654

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

9310

18620

27929

37239

46549

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21148

42296

63444

84592

105740

<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:

0.759

AC:

115237

AN:

151730

Hom.:

46068

Cov.:

AF XY:

0.757

AC XY:

56137

AN XY:

74154

show subpopulations

African (AFR)

AF:

0.567

AC:

23393

AN:

41272

American (AMR)

AF:

0.694

AC:

10574

AN:

15228

Ashkenazi Jewish (ASJ)

AF:

0.859

AC:

2981

AN:

3470

East Asian (EAS)

AF:

0.310

AC:

1588

AN:

5128

South Asian (SAS)

AF:

0.769

AC:

3707

AN:

4818

European-Finnish (FIN)

AF:

0.929

AC:

9791

AN:

10536

Middle Eastern (MID)

AF:

0.813

AC:

239

AN:

294

European-Non Finnish (NFE)

AF:

0.890

AC:

60496

AN:

67972

Other (OTH)

AF:

0.782

AC:

1645

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1111

2222

3332

4443

5554

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

832

1664

2496

3328

4160

<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:

0.825

Hom.:

40455

Bravo

AF:

0.727

Asia WGS

AF:

0.628

AC:

2182

AN:

3478

EpiCase

AF:

0.886

EpiControl

AF:

0.888

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Jul 05, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.055

(source)

DANN

Benign

0.39

PhyloP100

-2.1

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over