2-26401975-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_145038.5(DRC1):c.-15C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.027 in 1,590,130 control chromosomes in the GnomAD database, including 746 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.021 (51 hom., cov: 32)
  • Exomes 𝑓: 0.028 (695 hom.)
• Consequence: DRC1 NM_145038.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.865

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 2-26401975-C-T is Benign according to our data. Variant chr2-26401975-C-T is described in ClinVar as [Benign]. Clinvar id is 1275914.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0582 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DRC1	NM_145038.5	c.-15C>T		5_prime_UTR_variant	1/17	ENST00000288710.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DRC1	ENST00000288710.7	c.-15C>T		5_prime_UTR_variant	1/17	2	NM_145038.5	P1
DRC1	ENST00000421869.5	c.-15C>T		5_prime_UTR_variant, NMD_transcript_variant	1/8	1
DRC1	ENST00000649059.1			upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.0206 AC: 3141 AN: 152158 Hom.: 51 Cov.: 32

Gnomad AFR AF: 0.00635

Gnomad AMI AF: 0.00659

Gnomad AMR AF: 0.0160

Gnomad ASJ AF: 0.0112

Gnomad EAS AF: 0.0638

Gnomad SAS AF: 0.0147

Gnomad FIN AF: 0.0180

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0286

Gnomad OTH AF: 0.0220

GnomAD3 exomes AF: 0.0233 AC: 4854 AN: 208666 Hom.: 74 AF XY: 0.0237 AC XY: 2677 AN XY: 113064

Gnomad AFR exome AF: 0.00507

Gnomad AMR exome AF: 0.0113

Gnomad ASJ exome AF: 0.0147

Gnomad EAS exome AF: 0.0622

Gnomad SAS exome AF: 0.0121

Gnomad FIN exome AF: 0.0179

Gnomad NFE exome AF: 0.0281

Gnomad OTH exome AF: 0.0274

GnomAD4 exome AF: 0.0277 AC: 39841 AN: 1437854 Hom.: 695 Cov.: 30 AF XY: 0.0274 AC XY: 19519 AN XY: 713018

Gnomad4 AFR exome AF: 0.00457

Gnomad4 AMR exome AF: 0.0119

Gnomad4 ASJ exome AF: 0.0127

Gnomad4 EAS exome AF: 0.0849

Gnomad4 SAS exome AF: 0.0134

Gnomad4 FIN exome AF: 0.0200

Gnomad4 NFE exome AF: 0.0289

Gnomad4 OTH exome AF: 0.0259

GnomAD4 genome AF: 0.0206 AC: 3138 AN: 152276 Hom.: 51 Cov.: 32 AF XY: 0.0200 AC XY: 1489 AN XY: 74452

Gnomad4 AFR AF: 0.00633

Gnomad4 AMR AF: 0.0159

Gnomad4 ASJ AF: 0.0112

Gnomad4 EAS AF: 0.0639

Gnomad4 SAS AF: 0.0145

Gnomad4 FIN AF: 0.0180

Gnomad4 NFE AF: 0.0286

Gnomad4 OTH AF: 0.0213

Alfa AF: 0.0223 Hom.: 10

Bravo AF: 0.0200

Asia WGS AF: 0.0480 AC: 166 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 06, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	5.0
Dann	Benign	0.64

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: rs9789650; hg19: chr2-26624843; COSMIC: COSV56530575;