Variant 2-26453340-G-A 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.1710G>A(p.Ala570=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00341 in 1,613,222 control chromosomes in the GnomAD database, including 142 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 75 hom., cov: 33)

Exomes 𝑓: 0.0019 ( 67 hom. )

Consequence

DRC1
NM_145038.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.45

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=-0.84).

BP6

Variant 2-26453340-G-A is Benign according to our data. Variant chr2-26453340-G-A is described in ClinVar as [Benign]. Clinvar id is 414293.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.45 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0572 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.1710G>A	p.Ala570=	synonymous_variant	14/17	ENST00000288710.7
DRC1	XM_047446339.1 linkuse as main transcript	c.690G>A	p.Ala230=	synonymous_variant	7/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
DRC1	ENST00000288710.7 linkuse as main transcript	c.1710G>A	p.Ala570=	synonymous_variant	14/17	2	NM_145038.5	P1
DRC1	ENST00000439066.2 linkuse as main transcript	n.440G>A		non_coding_transcript_exon_variant	5/5	3
DRC1	ENST00000649059.1 linkuse as main transcript	c.*673G>A		3_prime_UTR_variant, NMD_transcript_variant	13/16

Frequencies

GnomAD3 genomes

AF:

0.0174

AC:

2641

AN:

151700

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0589

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0106

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.000485

Gnomad OTH

AF:

0.0106

GnomAD3 exomes

AF:

0.00462

AC:

1149

AN:

248936

Hom.:

AF XY:

0.00343

AC XY:

462

AN XY:

134758

show subpopulations

Gnomad AFR exome

AF:

0.0578

Gnomad AMR exome

AF:

0.00396

Gnomad ASJ exome

AF:

0.00119

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000306

Gnomad OTH exome

AF:

0.00392

GnomAD4 exome

AF:

0.00195

AC:

2849

AN:

1461408

Hom.:

Cov.:

AF XY:

0.00170

AC XY:

1236

AN XY:

727076

show subpopulations

Gnomad4 AFR exome

AF:

0.0608

Gnomad4 AMR exome

AF:

0.00492

Gnomad4 ASJ exome

AF:

0.00115

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000186

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000219

Gnomad4 OTH exome

AF:

0.00484

GnomAD4 genome

AF:

0.0175

AC:

2659

AN:

151814

Hom.:

Cov.:

AF XY:

0.0170

AC XY:

1262

AN XY:

74240

show subpopulations

Gnomad4 AFR

AF:

0.0592

Gnomad4 AMR

AF:

0.0106

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000485

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.00931

Hom.:

Bravo

AF:

0.0199

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.000327

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 29, 2023	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 27, 2018	- -

Primary ciliary dyskinesia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.92

DANN

Benign

0.61

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