2-26453454-G-C

Variant names:

• chr2-26453454-G-C
• rs1402962
• NM_145038.5:c.1824G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_145038.5(DRC1):​c.1824G>C​(p.Glu608Asp) 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. 7/10 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. E608E) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: DRC1 NM_145038.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.901
• Publications: 10 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0566248).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRC1	NM_145038.5	c.1824G>C	p.Glu608Asp	missense_variant	Exon 14 of 17	ENST00000288710.7	NP_659475.2
DRC1	XM_047446339.1	c.804G>C	p.Glu268Asp	missense_variant	Exon 7 of 10		XP_047302295.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DRC1	ENST00000288710.7	c.1824G>C	p.Glu608Asp	missense_variant	Exon 14 of 17	2	NM_145038.5	ENSP00000288710.2
DRC1	ENST00000439066.2	n.554G>C		non_coding_transcript_exon_variant	Exon 5 of 5	3
DRC1	ENST00000649059.1	n.*787G>C		non_coding_transcript_exon_variant	Exon 13 of 16			ENSP00000497543.1
DRC1	ENST00000649059.1	n.*787G>C		3_prime_UTR_variant	Exon 13 of 16			ENSP00000497543.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.067
DEOGEN2	Benign	0.0011	T
LIST_S2	Benign	0.36	T
MetaRNN	Benign	0.057	T
PhyloP100		-0.90
PROVEAN	Benign	-0.70	N
Sift	Benign	0.20	T
Sift4G	Benign	0.29	T
Vest4		0.075
gMVP		0.19

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: rs1402962; hg19: chr2-26676322;