Variant 2-26453527-G-T 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.1897G>T(p.Val633Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0918 in 1,613,792 control chromosomes in the GnomAD database, including 15,805 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.093 ( 1713 hom., cov: 32)

Exomes 𝑓: 0.092 ( 14092 hom. )

Consequence

DRC1
NM_145038.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.41

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=6.532371E-4).

BP6

Variant 2-26453527-G-T is Benign according to our data. Variant chr2-26453527-G-T is described in ClinVar as [Benign]. Clinvar id is 402798.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.576 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.1897G>T	p.Val633Phe	missense_variant	14/17	ENST00000288710.7	NP_659475.2
DRC1	XM_047446339.1 linkuse as main transcript	c.877G>T	p.Val293Phe	missense_variant	7/10		XP_047302295.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
DRC1	ENST00000288710.7 linkuse as main transcript	c.1897G>T	p.Val633Phe	missense_variant	14/17	2	NM_145038.5	ENSP00000288710	P1
DRC1	ENST00000649059.1 linkuse as main transcript	c.*860G>T		3_prime_UTR_variant, NMD_transcript_variant	13/16			ENSP00000497543
DRC1	ENST00000439066.2 linkuse as main transcript			downstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0934

AC:

14209

AN:

152090

Hom.:

1711

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0337

Gnomad AMI

AF:

0.0844

Gnomad AMR

AF:

0.235

Gnomad ASJ

AF:

0.0876

Gnomad EAS

AF:

0.594

Gnomad SAS

AF:

0.101

Gnomad FIN

AF:

0.0515

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0670

Gnomad OTH

AF:

0.0881

GnomAD3 exomes

AF:

0.145

AC:

36098

AN:

248512

Hom.:

6009

AF XY:

0.132

AC XY:

17743

AN XY:

134566

show subpopulations

Gnomad AFR exome

AF:

0.0330

Gnomad AMR exome

AF:

0.355

Gnomad ASJ exome

AF:

0.0857

Gnomad EAS exome

AF:

0.587

Gnomad SAS exome

AF:

0.0954

Gnomad FIN exome

AF:

0.0516

Gnomad NFE exome

AF:

0.0634

Gnomad OTH exome

AF:

0.102

GnomAD4 exome

AF:

0.0916

AC:

133916

AN:

1461588

Hom.:

14092

Cov.:

AF XY:

0.0905

AC XY:

65772

AN XY:

727074

show subpopulations

Gnomad4 AFR exome

AF:

0.0279

Gnomad4 AMR exome

AF:

0.338

Gnomad4 ASJ exome

AF:

0.0904

Gnomad4 EAS exome

AF:

0.615

Gnomad4 SAS exome

AF:

0.0971

Gnomad4 FIN exome

AF:

0.0519

Gnomad4 NFE exome

AF:

0.0662

Gnomad4 OTH exome

AF:

0.100

GnomAD4 genome

AF:

0.0934

AC:

14216

AN:

152204

Hom.:

1713

Cov.:

AF XY:

0.0982

AC XY:

7305

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.0337

Gnomad4 AMR

AF:

0.235

Gnomad4 ASJ

AF:

0.0876

Gnomad4 EAS

AF:

0.593

Gnomad4 SAS

AF:

0.101

Gnomad4 FIN

AF:

0.0515

Gnomad4 NFE

AF:

0.0670

Gnomad4 OTH

AF:

0.0872

Alfa

AF:

0.0785

Hom.:

1877

Bravo

AF:

0.110

TwinsUK

AF:

0.0607

AC:

225

ALSPAC

AF:

0.0690

AC:

266

ESP6500AA

AF:

0.0325

AC:

143

ESP6500EA

AF:

0.0679

AC:

584

ExAC

AF:

0.132

AC:

16023

Asia WGS

AF:

0.248

AC:

861

AN:

3478

EpiCase

AF:

0.0654

EpiControl

AF:

0.0645

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	clinical testing	GeneDx	Jul 09, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

Uncertain

0.48

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

Eigen

Pathogenic

0.70

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.77

MetaRNN

Benign

0.00065

MetaSVM

Benign

-0.92

MutationAssessor

Pathogenic

3.2

MutationTaster

Benign

0.0094

PrimateAI

Uncertain

0.52

PROVEAN

Uncertain

-3.9

REVEL

Benign

0.18

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0020

Polyphen

0.98

Vest4

0.24

MPC

0.39

ClinPred

0.040

GERP RS

5.0

Varity_R

0.46

gMVP

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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