rs4072407

chr2-26448676-A-G

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.1397-15A>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.772 in 1,612,870 control chromosomes in the GnomAD database, including 496,994 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.66 (37103 hom., cov: 33)
  • Exomes 𝑓: 0.78 (459891 hom.)
• Consequence: DRC1 NM_145038.5 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -2.30

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=-1.03).
• BP6: Variant 2-26448676-A-G is Benign according to our data. Variant chr2-26448676-A-G is described in ClinVar as [Benign]. Clinvar id is 262565.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.82 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DRC1	NM_145038.5	c.1397-15A>G		splice_polypyrimidine_tract_variant, intron_variant		ENST00000288710.7
DRC1	XM_047446339.1	c.377-15A>G		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DRC1	ENST00000288710.7	c.1397-15A>G		splice_polypyrimidine_tract_variant, intron_variant		2	NM_145038.5	P1
DRC1	ENST00000649059.1	c.*360-15A>G		splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant
DRC1	ENST00000439066.2	n.127-15A>G		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.664 AC: 101014 AN: 152044 Hom.: 37097 Cov.: 33

Gnomad AFR AF: 0.375

Gnomad AMI AF: 0.872

Gnomad AMR AF: 0.629

Gnomad ASJ AF: 0.821

Gnomad EAS AF: 0.263

Gnomad SAS AF: 0.723

Gnomad FIN AF: 0.904

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.825

Gnomad OTH AF: 0.695

GnomAD3 exomes AF: 0.714 AC: 179396 AN: 251128 Hom.: 68744 AF XY: 0.733 AC XY: 99488 AN XY: 135756

Gnomad AFR exome AF: 0.357

Gnomad AMR exome AF: 0.565

Gnomad ASJ exome AF: 0.816

Gnomad EAS exome AF: 0.266

Gnomad SAS exome AF: 0.737

Gnomad FIN exome AF: 0.903

Gnomad NFE exome AF: 0.830

Gnomad OTH exome AF: 0.768

GnomAD4 exome AF: 0.783 AC: 1143533 AN: 1460708 Hom.: 459891 Cov.: 35 AF XY: 0.784 AC XY: 570023 AN XY: 726662

Gnomad4 AFR exome AF: 0.354

Gnomad4 AMR exome AF: 0.576

Gnomad4 ASJ exome AF: 0.808

Gnomad4 EAS exome AF: 0.240

Gnomad4 SAS exome AF: 0.735

Gnomad4 FIN exome AF: 0.897

Gnomad4 NFE exome AF: 0.823

Gnomad4 OTH exome AF: 0.751

GnomAD4 genome AF: 0.664 AC: 101047 AN: 152162 Hom.: 37103 Cov.: 33 AF XY: 0.666 AC XY: 49579 AN XY: 74406

Gnomad4 AFR AF: 0.374

Gnomad4 AMR AF: 0.628

Gnomad4 ASJ AF: 0.821

Gnomad4 EAS AF: 0.264

Gnomad4 SAS AF: 0.722

Gnomad4 FIN AF: 0.904

Gnomad4 NFE AF: 0.826

Gnomad4 OTH AF: 0.697

Alfa AF: 0.795 Hom.: 79520

Bravo AF: 0.625

Asia WGS AF: 0.573 AC: 1989 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

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	-	- -

Primary ciliary dyskinesia Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Primary ciliary dyskinesia 21 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.0060
Dann	Benign	0.26

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs4072407; hg19: chr2-26671544; COSMIC: COSV56531656; COSMIC: COSV56531656;