rs116549039

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_145038.5(DRC1):c.36G>C(p.Pro12Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00165 in 1,612,076 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0087 ( 18 hom., cov: 32)

Exomes 𝑓: 0.00091 ( 16 hom. )

Consequence

DRC1
NM_145038.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.335

Publications

0 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=-0.63).

BP6

Variant 2-26402025-G-C is Benign according to our data. Variant chr2-26402025-G-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 241940.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.335 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00874 (1332/152326) while in subpopulation AFR AF = 0.0306 (1270/41568). AF 95% confidence interval is 0.0292. There are 18 homozygotes in GnomAd4. There are 641 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 18 AR,AD gene

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.36G>C	p.Pro12Pro	synonymous	Exon 1 of 17	NP_659475.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DRC1	ENST00000288710.7	TSL:2 MANE Select	c.36G>C	p.Pro12Pro	synonymous	Exon 1 of 17	ENSP00000288710.2
DRC1	ENST00000421869.5	TSL:1	n.36G>C		non_coding_transcript_exon	Exon 1 of 8	ENSP00000414375.1
DRC1	ENST00000649059.1		n.21G>C		non_coding_transcript_exon	Exon 1 of 16	ENSP00000497543.1

Frequencies

GnomAD3 genomes

AF:

0.00872

AC:

1327

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0305

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00249

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00669

GnomAD2 exomes

AF:

0.00223

AC:

547

AN:

245552

AF XY:

0.00160

show subpopulations

Gnomad AFR exome

AF:

0.0319

Gnomad AMR exome

AF:

0.000963

Gnomad ASJ exome

AF:

0.000201

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000814

Gnomad OTH exome

AF:

0.000835

GnomAD4 exome

AF:

0.000912

AC:

1332

AN:

1459750

Hom.:

Cov.:

AF XY:

0.000788

AC XY:

572

AN XY:

725928

show subpopulations

African (AFR)

AF:

0.0315

AC:

1055

AN:

33452

American (AMR)

AF:

0.00130

AC:

AN:

44594

Ashkenazi Jewish (ASJ)

AF:

0.000192

AC:

AN:

26070

East Asian (EAS)

AF:

0.00

AC:

AN:

39632

South Asian (SAS)

AF:

0.0000699

AC:

AN:

85784

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52872

Middle Eastern (MID)

AF:

0.00260

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.0000819

AC:

AN:

1111288

Other (OTH)

AF:

0.00169

AC:

102

AN:

60294

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

150

226

301

376

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

144

180

<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:

0.00874

AC:

1332

AN:

152326

Hom.:

Cov.:

AF XY:

0.00861

AC XY:

641

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.0306

AC:

1270

AN:

41568

American (AMR)

AF:

0.00248

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

68034

Other (OTH)

AF:

0.00662

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

127

190

254

317

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00277

Hom.:

Bravo

AF:

0.00989

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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

Jan 13, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Primary ciliary dyskinesia 21

Benign:1

May 03, 2022

Fulgent Genetics, Fulgent Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

3.0

(source)

DANN

Benign

0.53

PhyloP100

-0.34

PromoterAI

0.014

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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