rs35094910

chr2-26444286-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2 BP4_Strong BP6_Moderate BS1

The NM_145038.5(DRC1):c.1093G>A(p.Glu365Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000124 in 1,614,166 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00076 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000057 (0 hom.)
• Consequence: DRC1 NM_145038.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 6.98

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 Benign. Variant got -8 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.021653712).
• BP6: Variant 2-26444286-G-A is Benign according to our data. Variant chr2-26444286-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 454975.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000762 (116/152300) while in subpopulation AFR AF= 0.00265 (110/41570). AF 95% confidence interval is 0.00224. There are 0 homozygotes in gnomad4. There are 60 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DRC1	NM_145038.5	c.1093G>A	p.Glu365Lys	missense_variant	9/17	ENST00000288710.7
DRC1	XM_047446339.1	c.73G>A	p.Glu25Lys	missense_variant	2/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DRC1	ENST00000288710.7	c.1093G>A	p.Glu365Lys	missense_variant	9/17	2	NM_145038.5	P1

Frequencies

GnomAD3 genomes AF: 0.000762 AC: 116 AN: 152182 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00265

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000957

GnomAD3 exomes AF: 0.000167 AC: 42 AN: 251412 Hom.: 0 AF XY: 0.000110 AC XY: 15 AN XY: 135890

Gnomad AFR exome AF: 0.00240

Gnomad AMR exome AF: 0.0000578

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: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000575 AC: 84 AN: 1461866 Hom.: 0 Cov.: 32 AF XY: 0.0000440 AC XY: 32 AN XY: 727238

Gnomad4 AFR exome AF: 0.00224

Gnomad4 AMR exome AF: 0.0000895

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: 0.0000497

GnomAD4 genome AF: 0.000762 AC: 116 AN: 152300 Hom.: 0 Cov.: 32 AF XY: 0.000806 AC XY: 60 AN XY: 74474

Gnomad4 AFR AF: 0.00265

Gnomad4 AMR AF: 0.000262

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.000947

Alfa AF: 0.0000950 Hom.: 0

Bravo AF: 0.000922

ESP6500AA AF: 0.00363 AC: 16

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000206 AC: 25

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Primary ciliary dyskinesia Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 12, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.47
Cadd	Pathogenic	28
Dann	Pathogenic	1.0
DEOGEN2	Benign	0.060	T
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.022	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.9	M
MutationTaster	Benign	0.67	N
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.16
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.051	T
Polyphen		0.99	D
Vest4		0.39
MVP		0.50
MPC		0.36
ClinPred		0.17	T
GERP RS		5.4
Varity_R		0.33
gMVP		0.20

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: rs35094910; hg19: chr2-26667154;