rs142371860

Variant names:

• chr2-26421396-C-A
• rs142371860
• NM_145038.5:c.352C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-26421396-C-A
• chr2-26421396-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_145038.5(DRC1):​c.352C>A​(p.Gln118Lys) variant causes a missense 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. 16/22 in silico tools predict 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: 31)
• Consequence: DRC1 NM_145038.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.88
• Publications: 15 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20980433).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRC1	NM_145038.5	c.352C>A	p.Gln118Lys	missense_variant	Exon 3 of 17	ENST00000288710.7	NP_659475.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DRC1	ENST00000288710.7	c.352C>A	p.Gln118Lys	missense_variant	Exon 3 of 17	2	NM_145038.5	ENSP00000288710.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 31

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	22
DANN	Benign	0.83
DEOGEN2	Benign	0.0031	T
Eigen	Benign	-0.060
Eigen_PC	Benign	0.075
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		1.9
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.11
Sift	Benign	0.91	T
Sift4G	Benign	0.38	T
Polyphen		0.38	B
Vest4		0.45
MutPred		0.26		Gain of ubiquitination at Q118 (P = 0.0114);
MVP		0.40
MPC		0.11
ClinPred		0.45	T
GERP RS		5.4
Varity_R		0.44
gMVP		0.19
Mutation Taster		=91/9	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: rs142371860; hg19: chr2-26644264;