Variant 2-26450067-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_145038.5(DRC1):c.1581G>T(p.Arg527Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00049 in 1,613,362 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00063 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00047 ( 2 hom. )

Consequence

DRC1
NM_145038.5 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 1.28

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:

DRC1 (HGNC:):

DRC1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.014003605).

BP6

Variant 2-26450067-G-T is Benign according to our data. Variant chr2-26450067-G-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 454981.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DRC1	NM_145038.5 linkuse as main transcript	c.1581G>T	p.Arg527Ser	missense_variant	12/17	ENST00000288710.7	NP_659475.2	Q96MC2
DRC1	XM_047446339.1 linkuse as main transcript	c.561G>T	p.Arg187Ser	missense_variant	5/10		XP_047302295.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DRC1	ENST00000288710.7 linkuse as main transcript	c.1581G>T	p.Arg527Ser	missense_variant	12/17	2	NM_145038.5	ENSP00000288710.2	Q96MC2
DRC1	ENST00000439066.2 linkuse as main transcript	n.311G>T		non_coding_transcript_exon_variant	3/5	3
DRC1	ENST00000649059.1 linkuse as main transcript	n.*544G>T		non_coding_transcript_exon_variant	11/16			ENSP00000497543.1	A0A3B3IT12
DRC1	ENST00000649059.1 linkuse as main transcript	n.*544G>T		3_prime_UTR_variant	11/16			ENSP00000497543.1	A0A3B3IT12

Frequencies

GnomAD3 genomes

AF:

0.000631

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00621

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000397

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000804

AC:

201

AN:

249900

Hom.:

AF XY:

0.000688

AC XY:

AN XY:

135112

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000580

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00671

Gnomad NFE exome

AF:

0.000442

Gnomad OTH exome

AF:

0.000982

GnomAD4 exome

AF:

0.000475

AC:

694

AN:

1461182

Hom.:

Cov.:

AF XY:

0.000477

AC XY:

347

AN XY:

726858

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000672

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00660

Gnomad4 NFE exome

AF:

0.000287

Gnomad4 OTH exome

AF:

0.000331

GnomAD4 genome

AF:

0.000631

AC:

AN:

152180

Hom.:

Cov.:

AF XY:

0.000888

AC XY:

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00621

Gnomad4 NFE

AF:

0.000397

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000432

Hom.:

Bravo

AF:

0.000181

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000610

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.000416

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Jun 04, 2020

In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Primary ciliary dyskinesia

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 02, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.74

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.059

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.071

FATHMM_MKL

Benign

0.76

LIST_S2

Benign

0.83

M_CAP

Benign

0.0041

MetaRNN

Benign

0.014

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.1

PrimateAI

Benign

0.42

PROVEAN

Uncertain

-3.2

REVEL

Benign

0.23

Sift

Uncertain

0.0090

Sift4G

Uncertain

0.028

Polyphen

0.037

Vest4

0.69

MutPred

0.69

Gain of helix (P = 0.0496);

MVP

0.29

MPC

0.12

ClinPred

0.050

GERP RS

3.7

Varity_R

0.23

gMVP

0.54

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