Variant rs115095929 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_145038.5(DRC1):c.2147A>C(p.Gln716Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0121 in 1,613,754 control chromosomes in the GnomAD database, including 808 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.017 ( 109 hom., cov: 32)

Exomes 𝑓: 0.012 ( 699 hom. )

Consequence

DRC1
NM_145038.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 5.52

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003074348).

BP6

Variant 2-26455214-A-C is Benign according to our data. Variant chr2-26455214-A-C is described in ClinVar as [Benign]. Clinvar id is 414292.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-26455214-A-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DRC1	NM_145038.5 linkuse as main transcript	c.2147A>C	p.Gln716Pro	missense_variant	16/17	ENST00000288710.7	NP_659475.2	Q96MC2
DRC1	XM_047446339.1 linkuse as main transcript	c.1127A>C	p.Gln376Pro	missense_variant	9/10		XP_047302295.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DRC1	ENST00000288710.7 linkuse as main transcript	c.2147A>C	p.Gln716Pro	missense_variant	16/17	2	NM_145038.5	ENSP00000288710.2	Q96MC2
DRC1	ENST00000649059.1 linkuse as main transcript	n.*1110A>C		non_coding_transcript_exon_variant	15/16			ENSP00000497543.1	A0A3B3IT12
DRC1	ENST00000649059.1 linkuse as main transcript	n.*1110A>C		3_prime_UTR_variant	15/16			ENSP00000497543.1	A0A3B3IT12

Frequencies

GnomAD3 genomes

AF:

0.0174

AC:

2645

AN:

152182

Hom.:

108

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00352

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0552

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0505

Gnomad SAS

AF:

0.00394

Gnomad FIN

AF:

0.0916

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00547

Gnomad OTH

AF:

0.0153

GnomAD3 exomes

AF:

0.0330

AC:

8281

AN:

250808

Hom.:

515

AF XY:

0.0272

AC XY:

3696

AN XY:

135692

show subpopulations

Gnomad AFR exome

AF:

0.00210

Gnomad AMR exome

AF:

0.131

Gnomad ASJ exome

AF:

0.000596

Gnomad EAS exome

AF:

0.0505

Gnomad SAS exome

AF:

0.00255

Gnomad FIN exome

AF:

0.0883

Gnomad NFE exome

AF:

0.00583

Gnomad OTH exome

AF:

0.0220

GnomAD4 exome

AF:

0.0116

AC:

16911

AN:

1461454

Hom.:

699

Cov.:

AF XY:

0.0106

AC XY:

7734

AN XY:

726992

show subpopulations

Gnomad4 AFR exome

AF:

0.00161

Gnomad4 AMR exome

AF:

0.123

Gnomad4 ASJ exome

AF:

0.000459

Gnomad4 EAS exome

AF:

0.0426

Gnomad4 SAS exome

AF:

0.00320

Gnomad4 FIN exome

AF:

0.0838

Gnomad4 NFE exome

AF:

0.00377

Gnomad4 OTH exome

AF:

0.0121

GnomAD4 genome

AF:

0.0174

AC:

2649

AN:

152300

Hom.:

109

Cov.:

AF XY:

0.0215

AC XY:

1599

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.00351

Gnomad4 AMR

AF:

0.0553

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0510

Gnomad4 SAS

AF:

0.00394

Gnomad4 FIN

AF:

0.0916

Gnomad4 NFE

AF:

0.00547

Gnomad4 OTH

AF:

0.0152

Alfa

AF:

0.00557

Hom.:

Bravo

AF:

0.0173

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00182

AC:

ESP6500AA

AF:

0.00409

AC:

ESP6500EA

AF:

0.00302

AC:

ExAC

AF:

0.0269

AC:

3268

Asia WGS

AF:

0.0370

AC:

129

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 05, 2018	- -

Primary ciliary dyskinesia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.46

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.10

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.72

MetaRNN

Benign

0.0031

MetaSVM

Benign

-0.93

MutationAssessor

Pathogenic

3.0

PrimateAI

Benign

0.35

PROVEAN

Uncertain

-3.4

REVEL

Benign

0.26

Sift

Uncertain

0.012

Sift4G

Benign

0.063

Polyphen

0.98

Vest4

0.21

MPC

0.27

ClinPred

0.037

GERP RS

4.2

Varity_R

0.92

gMVP

0.57

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over