2-26454783-A-T

Position:

• chr2-26454783-A-T

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_145038.5(DRC1):​c.2056A>T​(p.Lys686Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DRC1 NM_145038.5 stop_gained
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 2.79

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 Pathogenic. Variant got 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 2-26454783-A-T is Pathogenic according to our data. Variant chr2-26454783-A-T is described in ClinVar as [Pathogenic]. Clinvar id is 55839.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DRC1	NM_145038.5	c.2056A>T	p.Lys686Ter	stop_gained	15/17	ENST00000288710.7	NP_659475.2
DRC1	XM_047446339.1	c.1036A>T	p.Lys346Ter	stop_gained	8/10		XP_047302295.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DRC1	ENST00000288710.7	c.2056A>T	p.Lys686Ter	stop_gained	15/17	2	NM_145038.5	ENSP00000288710	P1
DRC1	ENST00000649059.1	c.*1019A>T		3_prime_UTR_variant, NMD_transcript_variant	14/16			ENSP00000497543

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Primary ciliary dyskinesia 21 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Mar 01, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.63	D
BayesDel_noAF	Pathogenic	0.62
CADD	Pathogenic	40
DANN	Uncertain	1.0
Eigen	Pathogenic	0.72
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Uncertain	0.95	D
MutationTaster	Benign	1.0	A
Vest4		0.54
GERP RS		5.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs587776997; hg19: chr2-26677651;