rs878855222

Variant names:

• chr2-26453335-CAGGCGAGCATGGAGA-C
• rs878855222
• NM_145038.5:c.1720_1734delAAGGCGAGCATGGAG

Your query was ambiguous. Multiple possible variants found:

• chr2-26453335-CAGGCGAGCATGGAGA-C
• chr2-26453335-CAGGCGAGCATGGAGA-CAGGCGAGCATGGAGAAGGCGAGCATGGAGA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 2P and 10B. PM4 BP6_Moderate BS1 BS2

The NM_145038.5(DRC1):​c.1720_1734delAAGGCGAGCATGGAG​(p.Lys574_Glu578del) variant causes a conservative 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. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. 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 conservative_inframe_deletion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.571
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 21

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: ClinGen, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• spermatogenic failure 80

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -8 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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145038.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRC1	NM_145038.5	MANE Select	c.1720_1734delAAGGCGAGCATGGAG	p.Lys574_Glu578del	conservative_inframe_deletion	Exon 14 of 17	NP_659475.2	Q96MC2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRC1	ENST00000288710.7	TSL:2 MANE Select	c.1720_1734delAAGGCGAGCATGGAG	p.Lys574_Glu578del	conservative_inframe_deletion	Exon 14 of 17	ENSP00000288710.2	Q96MC2
	DRC1	ENST00000868388.1		c.1645_1659delAAGGCGAGCATGGAG	p.Lys549_Glu553del	conservative_inframe_deletion	Exon 14 of 17	ENSP00000538447.1
	DRC1	ENST00000941553.1		c.1423_1437delAAGGCGAGCATGGAG	p.Lys475_Glu479del	conservative_inframe_deletion	Exon 12 of 15	ENSP00000611612.1

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

GnomAD2 exomes AF: 0.000442 AC: 110 AN: 248928 AF XY: 0.000371

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 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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00541 AC: 181 AN: 33480

American (AMR) AF: 0.000201 AC: 9 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000812 AC: 7 AN: 86226

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000809 AC: 9 AN: 1112008

Other (OTH) AF: 0.000480 AC: 29 AN: 60392

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

African (AFR) AF: 0.00611 AC: 254 AN: 41552

American (AMR) AF: 0.000784 AC: 12 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68034

Other (OTH) AF: 0.00142 AC: 3 AN: 2112

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00196

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Primary ciliary dyskinesia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.57
Mutation Taster		=158/42	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs878855222; hg19: chr2-26676203; COSMIC: COSV106083818; COSMIC: COSV106083818;