rs878855222

chr2-26453335-CAGGCGAGCATGGAGA-Cchr2-26453335-CAGGCGAGCATGGAGA-CAGGCGAGCATGGAGAAGGCGAGCATGGAGA

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM4 BP6_Moderate BS1

The NM_145038.5(DRC1):c.1720_1734del(p.Lys574_Glu578del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000312 in 1,614,126 control chromosomes in the GnomAD database, including 3 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0018 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00016 (2 hom.)
• Consequence: DRC1 NM_145038.5 inframe_deletion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.571

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 -4 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_145038.5.
• BP6: Variant 2-26453335-CAGGCGAGCATGGAGA-C is Benign according to our data. Variant chr2-26453335-CAGGCGAGCATGGAGA-C is described in ClinVar as [Likely_benign]. Clinvar id is 241936.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00177 (269/152300) while in subpopulation AFR AF= 0.00611 (254/41552). AF 95% confidence interval is 0.0055. There are 1 homozygotes in gnomad4. There are 133 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.1720_1734del	p.Lys574_Glu578del	inframe_deletion	14/17	ENST00000288710.7
DRC1	XM_047446339.1	c.700_714del	p.Lys234_Glu238del	inframe_deletion	7/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DRC1	ENST00000288710.7	c.1720_1734del	p.Lys574_Glu578del	inframe_deletion	14/17	2	NM_145038.5	P1
DRC1	ENST00000439066.2	n.450_464del		non_coding_transcript_exon_variant	5/5	3
DRC1	ENST00000649059.1	c.*683_*697del		3_prime_UTR_variant, NMD_transcript_variant	13/16

Frequencies

GnomAD3 genomes AF: 0.00175 AC: 267 AN: 152182 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00608

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000785

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: 0.00144

GnomAD3 exomes AF: 0.000442 AC: 110 AN: 248928 Hom.: 0 AF XY: 0.000371 AC XY: 50 AN XY: 134746

Gnomad AFR exome AF: 0.00622

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000180

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.000161 AC: 235 AN: 1461826 Hom.: 2 AF XY: 0.000110 AC XY: 80 AN XY: 727214

Gnomad4 AFR exome AF: 0.00541

Gnomad4 AMR exome AF: 0.000201

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000812

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000809

Gnomad4 OTH exome AF: 0.000480

GnomAD4 genome AF: 0.00177 AC: 269 AN: 152300 Hom.: 1 Cov.: 32 AF XY: 0.00179 AC XY: 133 AN XY: 74464

Gnomad4 AFR AF: 0.00611

Gnomad4 AMR AF: 0.000784

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: 0.00142

Bravo AF: 0.00196

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

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

Dec 27, 2023

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs878855222; hg19: chr2-26676203;