2-26453454-G-T

Position:

• chr2-26453454-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_145038.5(DRC1):​c.1824G>T​(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.

• Frequency: Genomes: not found (cov: 33)
• Consequence: DRC1 NM_145038.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.901

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 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.056543052).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DRC1	NM_145038.5	c.1824G>T	p.Glu608Asp	missense_variant	14/17	ENST00000288710.7	NP_659475.2
DRC1	XM_047446339.1	c.804G>T	p.Glu268Asp	missense_variant	7/10		XP_047302295.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DRC1	ENST00000288710.7	c.1824G>T	p.Glu608Asp	missense_variant	14/17	2	NM_145038.5	ENSP00000288710.2
DRC1	ENST00000439066.2	n.554G>T		non_coding_transcript_exon_variant	5/5	3
DRC1	ENST00000649059.1	n.*787G>T		non_coding_transcript_exon_variant	13/16			ENSP00000497543.1
DRC1	ENST00000649059.1	n.*787G>T		3_prime_UTR_variant	13/16			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	-0.92
CADD	Benign	0.064
DEOGEN2	Benign	0.0011	T
LIST_S2	Benign	0.36	T
MetaRNN	Benign	0.057	T
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

Publications

LitVar

Other links and lift over

dbSNP: rs1402962; hg19: chr2-26676322;