rs149007147

Variant names:

• chr2-26448693-G-A
• NM_145038.5:c.1399G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-26448693-G-A
• chr2-26448693-G-C
• chr2-26448693-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.1399G>A​(p.Glu467Lys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,766 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E467Q) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: DRC1 NM_145038.5 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.733

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 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=0.052675456).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRC1	NM_145038.5	c.1399G>A	p.Glu467Lys	missense_variant, splice_region_variant	Exon 11 of 17	ENST00000288710.7	NP_659475.2
DRC1	XM_047446339.1	c.379G>A	p.Glu127Lys	missense_variant, splice_region_variant	Exon 4 of 10		XP_047302295.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DRC1	ENST00000288710.7	c.1399G>A	p.Glu467Lys	missense_variant, splice_region_variant	Exon 11 of 17	2	NM_145038.5	ENSP00000288710.2
DRC1	ENST00000439066.2	n.129G>A		splice_region_variant, non_coding_transcript_exon_variant	Exon 2 of 5	3
DRC1	ENST00000649059.1	n.*362G>A		splice_region_variant, non_coding_transcript_exon_variant	Exon 10 of 16			ENSP00000497543.1
DRC1	ENST00000649059.1	n.*362G>A		3_prime_UTR_variant	Exon 10 of 16			ENSP00000497543.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461766 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727166

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.00046	T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.19
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.053	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.68	N
REVEL	Benign	0.057
Sift	Benign	0.37	T
Sift4G	Benign	0.11	T
Polyphen		0.0030	B
Vest4		0.23
MutPred		0.32		Gain of ubiquitination at E467 (P = 9e-04);
MVP		0.12
MPC		0.064
ClinPred		0.31	T
GERP RS		4.7
Varity_R		0.050
gMVP		0.20

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-26671561;