2-26456517-A-T

Variant names:

• chr2-26456517-A-T
• rs151184011
• NM_145038.5:c.2223A>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PM4

The NM_145038.5(DRC1):​c.2223A>T​(p.Ter741Cysext*?) variant causes a stop lost change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: DRC1 NM_145038.5 stop_lost
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.375
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 21

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• spermatogenic failure 80

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Stoplost variant in NM_145038.5 Downstream stopcodon found after 763 codons.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRC1	NM_145038.5	c.2223A>T	p.Ter741Cysext*?	stop_lost	Exon 17 of 17	ENST00000288710.7	NP_659475.2
DRC1	XM_047446339.1	c.1203A>T	p.Ter401Cysext*?	stop_lost	Exon 10 of 10		XP_047302295.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DRC1	ENST00000288710.7	c.2223A>T	p.Ter741Cysext*?	stop_lost	Exon 17 of 17	2	NM_145038.5	ENSP00000288710.2
DRC1	ENST00000649059.1	n.*1186A>T		non_coding_transcript_exon_variant	Exon 16 of 16			ENSP00000497543.1
DRC1	ENST00000649059.1	n.*1186A>T		3_prime_UTR_variant	Exon 16 of 16			ENSP00000497543.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 1

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	11
DANN	Benign	0.88
Eigen	Uncertain	0.22
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.19	N
PhyloP100		0.38
Vest4		0.037
GERP RS		0.41
Mutation Taster		=183/17	polymorphism

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

Other links and lift over

dbSNP: rs151184011; hg19: chr2-26679385;