Variant 2-26456494-G-A 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.2200G>A(p.Val734Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0536 in 1,614,084 control chromosomes in the GnomAD database, including 2,640 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.042 ( 182 hom., cov: 33)

Exomes 𝑓: 0.055 ( 2458 hom. )

Consequence

DRC1
NM_145038.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.19

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=0.0021615028).

BP6

Variant 2-26456494-G-A is Benign according to our data. Variant chr2-26456494-G-A is described in ClinVar as [Benign]. Clinvar id is 402799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0604 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DRC1	NM_145038.5 link	c.2200G>A	p.Val734Met	missense_variant	17/17	ENST00000288710.7	NP_659475.2	Q96MC2
DRC1	XM_047446339.1 link	c.1180G>A	p.Val394Met	missense_variant	10/10		XP_047302295.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DRC1	ENST00000288710.7 link	c.2200G>A	p.Val734Met	missense_variant	17/17	2	NM_145038.5	ENSP00000288710.2	Q96MC2
DRC1	ENST00000649059.1 link	n.*1163G>A		non_coding_transcript_exon_variant	16/16			ENSP00000497543.1	A0A3B3IT12
DRC1	ENST00000649059.1 link	n.*1163G>A		3_prime_UTR_variant	16/16			ENSP00000497543.1	A0A3B3IT12

Frequencies

GnomAD3 genomes

AF:

0.0419

AC:

6378

AN:

152190

Hom.:

182

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0116

Gnomad AMI

AF:

0.0549

Gnomad AMR

AF:

0.0561

Gnomad ASJ

AF:

0.0881

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0217

Gnomad FIN

AF:

0.0210

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0619

Gnomad OTH

AF:

0.0607

GnomAD3 exomes

AF:

0.0411

AC:

10326

AN:

251352

Hom.:

291

AF XY:

0.0423

AC XY:

5753

AN XY:

135852

show subpopulations

Gnomad AFR exome

AF:

0.00886

Gnomad AMR exome

AF:

0.0279

Gnomad ASJ exome

AF:

0.0910

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0224

Gnomad FIN exome

AF:

0.0219

Gnomad NFE exome

AF:

0.0600

Gnomad OTH exome

AF:

0.0521

GnomAD4 exome

AF:

0.0548

AC:

80152

AN:

1461776

Hom.:

2458

Cov.:

AF XY:

0.0541

AC XY:

39305

AN XY:

727196

show subpopulations

Gnomad4 AFR exome

AF:

0.00929

Gnomad4 AMR exome

AF:

0.0300

Gnomad4 ASJ exome

AF:

0.0894

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0226

Gnomad4 FIN exome

AF:

0.0224

Gnomad4 NFE exome

AF:

0.0625

Gnomad4 OTH exome

AF:

0.0533

GnomAD4 genome

AF:

0.0418

AC:

6374

AN:

152308

Hom.:

182

Cov.:

AF XY:

0.0395

AC XY:

2943

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.0116

Gnomad4 AMR

AF:

0.0560

Gnomad4 ASJ

AF:

0.0881

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0213

Gnomad4 FIN

AF:

0.0210

Gnomad4 NFE

AF:

0.0619

Gnomad4 OTH

AF:

0.0601

Alfa

AF:

0.0575

Hom.:

432

Bravo

AF:

0.0437

TwinsUK

AF:

0.0663

AC:

246

ALSPAC

AF:

0.0542

AC:

209

ESP6500AA

AF:

0.00931

AC:

ESP6500EA

AF:

0.0640

AC:

550

ExAC

AF:

0.0406

AC:

4929

Asia WGS

AF:

0.0110

AC:

AN:

3478

EpiCase

AF:

0.0638

EpiControl

AF:

0.0628

ClinVar

Significance: Benign

Submissions summary: Benign:4

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 09, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

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

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

Benign

0.19

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0019

Eigen

Benign

-0.094

Eigen_PC

Benign

0.024

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.74

MetaRNN

Benign

0.0022

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.0

PrimateAI

Benign

0.48

PROVEAN

Benign

-0.94

REVEL

Benign

0.070

Sift

Benign

0.18

Sift4G

Benign

0.19

Polyphen

0.063

Vest4

0.090

MPC

0.15

ClinPred

0.024

GERP RS

4.8

Varity_R

0.082

gMVP

0.19

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