2-26453380-T-C

Position:

• chr2-26453380-T-C

Variant summary

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

The NM_145038.5(DRC1):​c.1750T>C​(p.Ser584Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. 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. S584T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: DRC1 NM_145038.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.905

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=0.048135966).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DRC1	NM_145038.5	c.1750T>C	p.Ser584Pro	missense_variant	14/17	ENST00000288710.7	NP_659475.2
DRC1	XM_047446339.1	c.730T>C	p.Ser244Pro	missense_variant	7/10		XP_047302295.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DRC1	ENST00000288710.7	c.1750T>C	p.Ser584Pro	missense_variant	14/17	2	NM_145038.5	ENSP00000288710.2
DRC1	ENST00000439066.2	n.480T>C		non_coding_transcript_exon_variant	5/5	3
DRC1	ENST00000649059.1	n.*713T>C		non_coding_transcript_exon_variant	13/16			ENSP00000497543.1
DRC1	ENST00000649059.1	n.*713T>C		3_prime_UTR_variant	13/16			ENSP00000497543.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000402 AC: 1 AN: 248990 Hom.: 0 AF XY: 0.00000742 AC XY: 1 AN XY: 134792

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461868 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727230

Gnomad4 AFR exome AF: 0.0000299

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.55
DANN	Benign	0.77
DEOGEN2	Benign	0.0019	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0044	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.017
Sift	Benign	0.044	D
Sift4G	Benign	0.10	T
Polyphen		0.0050	B
Vest4		0.046
MutPred		0.27		Loss of phosphorylation at S584 (P = 0.0037);
MVP		0.030
MPC		0.069
ClinPred		0.066	T
GERP RS		-9.5
Varity_R		0.22
gMVP		0.13

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: rs147712523; hg19: chr2-26676248;