dbSNP rs9789650: DRC1:c.-15C>T (chr2-26401975-C-T) – ACMG Classification: Benign (-20 pts)

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.-15C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.027 in 1,590,130 control chromosomes in the GnomAD database, including 746 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.021 ( 51 hom., cov: 32)

Exomes 𝑓: 0.028 ( 695 hom. )

Consequence

DRC1
NM_145038.5 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.865

Publications

5 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, Ambry Genetics, G2P, 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 (BayesDel_noAF=-0.8).

BP6

Variant 2-26401975-C-T is Benign according to our data. Variant chr2-26401975-C-T is described in ClinVar as Benign. ClinVar VariationId is 1275914.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0582 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.-15C>T		5_prime_UTR	Exon 1 of 17	NP_659475.2	Q96MC2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DRC1	ENST00000288710.7	TSL:2 MANE Select	c.-15C>T	5_prime_UTR	Exon 1 of 17	ENSP00000288710.2	Q96MC2
DRC1	ENST00000421869.5	TSL:1	n.-15C>T	non_coding_transcript_exon	Exon 1 of 8	ENSP00000414375.1	F8WE02
DRC1	ENST00000421869.5	TSL:1	n.-15C>T	5_prime_UTR	Exon 1 of 8	ENSP00000414375.1	F8WE02

Frequencies

GnomAD3 genomes

AF:

0.0206

AC:

3141

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00635

Gnomad AMI

AF:

0.00659

Gnomad AMR

AF:

0.0160

Gnomad ASJ

AF:

0.0112

Gnomad EAS

AF:

0.0638

Gnomad SAS

AF:

0.0147

Gnomad FIN

AF:

0.0180

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0286

Gnomad OTH

AF:

0.0220

GnomAD2 exomes

AF:

0.0233

AC:

4854

AN:

208666

AF XY:

0.0237

show subpopulations

Gnomad AFR exome

AF:

0.00507

Gnomad AMR exome

AF:

0.0113

Gnomad ASJ exome

AF:

0.0147

Gnomad EAS exome

AF:

0.0622

Gnomad FIN exome

AF:

0.0179

Gnomad NFE exome

AF:

0.0281

Gnomad OTH exome

AF:

0.0274

GnomAD4 exome

AF:

0.0277

AC:

39841

AN:

1437854

Hom.:

695

Cov.:

AF XY:

0.0274

AC XY:

19519

AN XY:

713018

show subpopulations

African (AFR)

AF:

0.00457

AC:

151

AN:

33028

American (AMR)

AF:

0.0119

AC:

492

AN:

41366

Ashkenazi Jewish (ASJ)

AF:

0.0127

AC:

323

AN:

25496

East Asian (EAS)

AF:

0.0849

AC:

3273

AN:

38568

South Asian (SAS)

AF:

0.0134

AC:

1106

AN:

82698

European-Finnish (FIN)

AF:

0.0200

AC:

1019

AN:

50826

Middle Eastern (MID)

AF:

0.0258

AC:

147

AN:

5700

European-Non Finnish (NFE)

AF:

0.0289

AC:

31789

AN:

1100698

Other (OTH)

AF:

0.0259

AC:

1541

AN:

59474

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

1987

3974

5962

7949

9936

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1248

2496

3744

4992

6240

<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:

0.0206

AC:

3138

AN:

152276

Hom.:

Cov.:

AF XY:

0.0200

AC XY:

1489

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.00633

AC:

263

AN:

41558

American (AMR)

AF:

0.0159

AC:

244

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0112

AC:

AN:

3470

East Asian (EAS)

AF:

0.0639

AC:

330

AN:

5164

South Asian (SAS)

AF:

0.0145

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0180

AC:

191

AN:

10620

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0286

AC:

1942

AN:

68012

Other (OTH)

AF:

0.0213

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

162

324

486

648

810

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

160

200

<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:

0.0223

Hom.:

Bravo

AF:

0.0200

Asia WGS

AF:

0.0480

AC:

166

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

5.0

(source)

DANN

Benign

0.64

PhyloP100

-0.86

PromoterAI

0.073

Neutral

(source)

Mutation Taster

=300/0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over