rs78892546

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.1067C>T(p.Ala356Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00625 in 1,614,120 control chromosomes in the GnomAD database, including 336 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A356I) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0083 ( 26 hom., cov: 32)

Exomes 𝑓: 0.0060 ( 310 hom. )

Consequence

DRC1
NM_145038.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.530

Publications

11 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: DEFINITIVE, STRONG, MODERATE Submitted by: ClinGen, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
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

new If you want to explore the variant's impact on the transcript NM_145038.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0024882853).

BP6

Variant 2-26444260-C-T is Benign according to our data. Variant chr2-26444260-C-T is described in ClinVar as Benign. ClinVar VariationId is 414283.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0713 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRC1	NM_145038.5	MANE Select	c.1067C>T	p.Ala356Val	missense	Exon 9 of 17	NP_659475.2	Q96MC2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DRC1	ENST00000288710.7	TSL:2 MANE Select	c.1067C>T	p.Ala356Val	missense	Exon 9 of 17	ENSP00000288710.2	Q96MC2
DRC1	ENST00000421869.5	TSL:1	n.*380C>T		non_coding_transcript_exon	Exon 7 of 8	ENSP00000414375.1	F8WE02
DRC1	ENST00000421869.5	TSL:1	n.*380C>T		3_prime_UTR	Exon 7 of 8	ENSP00000414375.1	F8WE02

Frequencies

GnomAD3 genomes

AF:

0.00834

AC:

1269

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0119

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00196

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.0676

Gnomad SAS

AF:

0.0775

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00335

GnomAD2 exomes

AF:

0.0143

AC:

3593

AN:

251320

AF XY:

0.0164

show subpopulations

Gnomad AFR exome

AF:

0.0113

Gnomad AMR exome

AF:

0.00203

Gnomad ASJ exome

AF:

0.000893

Gnomad EAS exome

AF:

0.0639

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000202

Gnomad OTH exome

AF:

0.00816

GnomAD4 exome

AF:

0.00603

AC:

8811

AN:

1461834

Hom.:

310

Cov.:

AF XY:

0.00770

AC XY:

5602

AN XY:

727220

show subpopulations

African (AFR)

AF:

0.0120

AC:

401

AN:

33474

American (AMR)

AF:

0.00215

AC:

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.000459

AC:

AN:

26134

East Asian (EAS)

AF:

0.0481

AC:

1908

AN:

39700

South Asian (SAS)

AF:

0.0658

AC:

5677

AN:

86250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53404

Middle Eastern (MID)

AF:

0.00156

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000872

AC:

AN:

1112002

Other (OTH)

AF:

0.0101

AC:

611

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

465

930

1396

1861

2326

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

134

268

402

536

670

<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:

0.00835

AC:

1271

AN:

152286

Hom.:

Cov.:

AF XY:

0.00974

AC XY:

725

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.0119

AC:

495

AN:

41552

American (AMR)

AF:

0.00196

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00144

AC:

AN:

3466

East Asian (EAS)

AF:

0.0672

AC:

348

AN:

5182

South Asian (SAS)

AF:

0.0778

AC:

375

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

68036

Other (OTH)

AF:

0.00520

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

125

187

250

312

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<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:

0.00432

Hom.:

Bravo

AF:

0.00725

Asia WGS

AF:

0.0600

AC:

207

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000178

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Primary ciliary dyskinesia (1)

Primary ciliary dyskinesia 21 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.68

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.031

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.75

MetaRNN

Benign

0.0025

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.2

PhyloP100

0.53

PrimateAI

Benign

0.30

PROVEAN

Benign

-2.1

REVEL

Benign

0.061

Sift

Benign

0.18

Sift4G

Benign

0.22

Varity_R

0.082

gMVP

0.070

Mutation Taster

=94/6

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.15

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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

Computational scores

Splicing

Publications

Other links and lift over