Variant 2-26424409-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_145038.5(DRC1):c.495T>G(p.Ala165=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.842 in 1,613,406 control chromosomes in the GnomAD database, including 585,512 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. A165A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.76 ( 46068 hom., cov: 29)

Exomes 𝑓: 0.85 ( 539444 hom. )

Consequence

DRC1
NM_145038.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -2.06

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 2-26424409-T-G is Benign according to our data. Variant chr2-26424409-T-G is described in ClinVar as [Benign]. Clinvar id is 262566.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.06 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.884 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.495T>G	p.Ala165=	synonymous_variant	4/17	ENST00000288710.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DRC1	ENST00000288710.7 linkuse as main transcript	c.495T>G	p.Ala165=	synonymous_variant	4/17	2	NM_145038.5	P1

Frequencies

GnomAD3 genomes

AF:

0.760

AC:

115199

AN:

151614

Hom.:

46066

Cov.:

show subpopulations

Gnomad AFR

AF:

0.567

Gnomad AMI

AF:

0.906

Gnomad AMR

AF:

0.695

Gnomad ASJ

AF:

0.859

Gnomad EAS

AF:

0.309

Gnomad SAS

AF:

0.771

Gnomad FIN

AF:

0.929

Gnomad MID

AF:

0.816

Gnomad NFE

AF:

0.890

Gnomad OTH

AF:

0.781

GnomAD3 exomes

AF:

0.774

AC:

194160

AN:

250974

Hom.:

79380

AF XY:

0.790

AC XY:

107173

AN XY:

135662

show subpopulations

Gnomad AFR exome

AF:

0.554

Gnomad AMR exome

AF:

0.600

Gnomad ASJ exome

AF:

0.858

Gnomad EAS exome

AF:

0.305

Gnomad SAS exome

AF:

0.782

Gnomad FIN exome

AF:

0.929

Gnomad NFE exome

AF:

0.892

Gnomad OTH exome

AF:

0.826

GnomAD4 exome

AF:

0.850

AC:

1243105

AN:

1461676

Hom.:

539444

Cov.:

AF XY:

0.851

AC XY:

618458

AN XY:

727130

show subpopulations

Gnomad4 AFR exome

AF:

0.555

Gnomad4 AMR exome

AF:

0.614

Gnomad4 ASJ exome

AF:

0.852

Gnomad4 EAS exome

AF:

0.306

Gnomad4 SAS exome

AF:

0.780

Gnomad4 FIN exome

AF:

0.926

Gnomad4 NFE exome

AF:

0.892

Gnomad4 OTH exome

AF:

0.822

GnomAD4 genome

AF:

0.759

AC:

115237

AN:

151730

Hom.:

46068

Cov.:

AF XY:

0.757

AC XY:

56137

AN XY:

74154

show subpopulations

Gnomad4 AFR

AF:

0.567

Gnomad4 AMR

AF:

0.694

Gnomad4 ASJ

AF:

0.859

Gnomad4 EAS

AF:

0.310

Gnomad4 SAS

AF:

0.769

Gnomad4 FIN

AF:

0.929

Gnomad4 NFE

AF:

0.890

Gnomad4 OTH

AF:

0.782

Alfa

AF:

0.844

Hom.:

20879

Bravo

AF:

0.727

Asia WGS

AF:

0.628

AC:

2182

AN:

3478

EpiCase

AF:

0.886

EpiControl

AF:

0.888

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
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

Invitae

Jan 31, 2024

- -

Primary ciliary dyskinesia 21

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

Cadd

Benign

0.055

Dann

Benign

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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