Variant rs74936036 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.172T>C(p.Tyr58His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00438 in 1,613,834 control chromosomes in the GnomAD database, including 247 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.023 ( 124 hom., cov: 32)

Exomes 𝑓: 0.0025 ( 123 hom. )

Consequence

DRC1
NM_145038.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.620

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=0.0016460717).

BP6

Variant 2-26414360-T-C is Benign according to our data. Variant chr2-26414360-T-C is described in ClinVar as [Benign]. Clinvar id is 414288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0741 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.172T>C	p.Tyr58His	missense_variant	2/17	ENST00000288710.7	NP_659475.2	Q96MC2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DRC1	ENST00000288710.7 linkuse as main transcript	c.172T>C	p.Tyr58His	missense_variant	2/17	2	NM_145038.5	ENSP00000288710.2	Q96MC2
DRC1	ENST00000421869.5 linkuse as main transcript	n.172T>C		non_coding_transcript_exon_variant	2/8	1		ENSP00000414375.1	F8WE02
DRC1	ENST00000649059.1 linkuse as main transcript	n.157T>C		non_coding_transcript_exon_variant	2/16			ENSP00000497543.1	A0A3B3IT12

Frequencies

GnomAD3 genomes

AF:

0.0225

AC:

3425

AN:

152042

Hom.:

123

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0764

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0125

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.000515

Gnomad OTH

AF:

0.0134

GnomAD3 exomes

AF:

0.00593

AC:

1489

AN:

251186

Hom.:

AF XY:

0.00425

AC XY:

577

AN XY:

135762

show subpopulations

Gnomad AFR exome

AF:

0.0765

Gnomad AMR exome

AF:

0.00467

Gnomad ASJ exome

AF:

0.00119

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000164

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000352

Gnomad OTH exome

AF:

0.00441

GnomAD4 exome

AF:

0.00249

AC:

3633

AN:

1461674

Hom.:

123

Cov.:

AF XY:

0.00218

AC XY:

1587

AN XY:

727150

show subpopulations

Gnomad4 AFR exome

AF:

0.0805

Gnomad4 AMR exome

AF:

0.00548

Gnomad4 ASJ exome

AF:

0.00115

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000244

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000221

Gnomad4 OTH exome

AF:

0.00599

GnomAD4 genome

AF:

0.0225

AC:

3430

AN:

152160

Hom.:

124

Cov.:

AF XY:

0.0218

AC XY:

1621

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.0763

Gnomad4 AMR

AF:

0.0124

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000515

Gnomad4 OTH

AF:

0.0132

Alfa

AF:

0.00417

Hom.:

Bravo

AF:

0.0257

ESP6500AA

AF:

0.0715

AC:

315

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00702

AC:

852

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 04, 2019	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Oct 09, 2023	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

0.17

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.79

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.00063

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.53

LIST_S2

Benign

0.57

MetaRNN

Benign

0.0016

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.9

PrimateAI

Uncertain

0.73

PROVEAN

Benign

0.030

REVEL

Benign

0.010

Sift

Benign

0.52

Sift4G

Benign

0.58

Polyphen

0.0010

Vest4

0.28

MVP

0.12

MPC

0.071

ClinPred

0.0039

GERP RS

1.4

Varity_R

0.031

gMVP

0.21

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