rs1054737

chr2-26456526-G-Achr2-26456526-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_145038.5(DRC1):c.*9G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0612 in 1,613,910 control chromosomes in the GnomAD database, including 3,534 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.046 (213 hom., cov: 33)
  • Exomes 𝑓: 0.063 (3321 hom.)
• Consequence: DRC1 NM_145038.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.830

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 2-26456526-G-A is Benign according to our data. Variant chr2-26456526-G-A is described in ClinVar as [Benign]. Clinvar id is 262563.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.064 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DRC1	NM_145038.5	c.*9G>A		3_prime_UTR_variant	17/17	ENST00000288710.7
DRC1	XM_047446339.1	c.*9G>A		3_prime_UTR_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DRC1	ENST00000288710.7	c.*9G>A		3_prime_UTR_variant	17/17	2	NM_145038.5	P1
DRC1	ENST00000649059.1	c.*1195G>A		3_prime_UTR_variant, NMD_transcript_variant	16/16

Frequencies

GnomAD3 genomes AF: 0.0462 AC: 7038 AN: 152204 Hom.: 213 Cov.: 33

Gnomad AFR AF: 0.0320

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.0339

Gnomad ASJ AF: 0.0412

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0244

Gnomad FIN AF: 0.0312

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0657

Gnomad OTH AF: 0.0435

GnomAD3 exomes AF: 0.0436 AC: 10962 AN: 251272 Hom.: 303 AF XY: 0.0449 AC XY: 6092 AN XY: 135814

Gnomad AFR exome AF: 0.0321

Gnomad AMR exome AF: 0.0243

Gnomad ASJ exome AF: 0.0401

Gnomad EAS exome AF: 0.000381

Gnomad SAS exome AF: 0.0247

Gnomad FIN exome AF: 0.0341

Gnomad NFE exome AF: 0.0651

Gnomad OTH exome AF: 0.0480

GnomAD4 exome AF: 0.0628 AC: 91745 AN: 1461590 Hom.: 3321 Cov.: 31 AF XY: 0.0613 AC XY: 44592 AN XY: 727086

Gnomad4 AFR exome AF: 0.0286

Gnomad4 AMR exome AF: 0.0248

Gnomad4 ASJ exome AF: 0.0403

Gnomad4 EAS exome AF: 0.00111

Gnomad4 SAS exome AF: 0.0254

Gnomad4 FIN exome AF: 0.0375

Gnomad4 NFE exome AF: 0.0727

Gnomad4 OTH exome AF: 0.0564

GnomAD4 genome AF: 0.0462 AC: 7039 AN: 152320 Hom.: 213 Cov.: 33 AF XY: 0.0433 AC XY: 3223 AN XY: 74480

Gnomad4 AFR AF: 0.0320

Gnomad4 AMR AF: 0.0339

Gnomad4 ASJ AF: 0.0412

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0244

Gnomad4 FIN AF: 0.0312

Gnomad4 NFE AF: 0.0656

Gnomad4 OTH AF: 0.0435

Alfa AF: 0.0577 Hom.: 410

Bravo AF: 0.0463

Asia WGS AF: 0.0140 AC: 53 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

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

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	0.43
Dann	Benign	0.93

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

Other links and lift over

dbSNP: rs1054737; hg19: chr2-26679394;