Variant rs78892546 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.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. 12/20 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:3

Conservation

PhyloP100: 0.530

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=0.0024882853).

BP6

Variant 2-26444260-C-T is Benign according to our data. Variant chr2-26444260-C-T is described in ClinVar as [Benign]. Clinvar id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DRC1	NM_145038.5 linkuse as main transcript	c.1067C>T	p.Ala356Val	missense_variant	9/17	ENST00000288710.7
DRC1	XM_047446339.1 linkuse as main transcript	c.47C>T	p.Ala16Val	missense_variant	2/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DRC1	ENST00000288710.7 linkuse as main transcript	c.1067C>T	p.Ala356Val	missense_variant	9/17	2	NM_145038.5	P1

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

GnomAD3 exomes

AF:

0.0143

AC:

3593

AN:

251320

Hom.:

141

AF XY:

0.0164

AC XY:

2227

AN XY:

135842

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 SAS exome

AF:

0.0680

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

Gnomad4 AFR exome

AF:

0.0120

Gnomad4 AMR exome

AF:

0.00215

Gnomad4 ASJ exome

AF:

0.000459

Gnomad4 EAS exome

AF:

0.0481

Gnomad4 SAS exome

AF:

0.0658

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000872

Gnomad4 OTH exome

AF:

0.0101

GnomAD4 genome

AF:

0.00835

AC:

1271

AN:

152286

Hom.:

Cov.:

AF XY:

0.00974

AC XY:

725

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.0119

Gnomad4 AMR

AF:

0.00196

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.0672

Gnomad4 SAS

AF:

0.0778

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00398

Hom.:

Bravo

AF:

0.00725

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.0102

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.0154

AC:

1873

Asia WGS

AF:

0.0600

AC:

207

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Primary ciliary dyskinesia 21

Benign:1

Benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Oct 21, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 19, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.68

CADD

Benign

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

MutationTaster

Benign

1.0

PrimateAI

Benign

0.30

PROVEAN

Benign

-2.1

REVEL

Benign

0.061

Sift

Benign

0.18

Sift4G

Benign

0.22

Polyphen

0.19

Vest4

0.079

MPC

0.12

ClinPred

0.0066

GERP RS

2.5

Varity_R

0.082

gMVP

0.070

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

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