2-26453454-G-A

Variant names:

• chr2-26453454-G-A
• rs1402962
• NM_145038.5:c.1824G>A

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_145038.5(DRC1):​c.1824G>A​(p.Glu608Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00101 in 1,614,146 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0052 (4 hom., cov: 33)
  • Exomes 𝑓: 0.00057 (5 hom.)
• Consequence: DRC1 NM_145038.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.901
• Publications: 10 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: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, G2P, PanelApp Australia, 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 2-26453454-G-A is Benign according to our data. Variant chr2-26453454-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 414290.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.901 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00522 (795/152316) while in subpopulation AFR AF = 0.0174 (725/41568). AF 95% confidence interval is 0.0164. There are 4 homozygotes in GnomAd4. There are 400 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRC1	NM_145038.5	c.1824G>A	p.Glu608Glu	synonymous_variant	Exon 14 of 17	ENST00000288710.7	NP_659475.2
DRC1	XM_047446339.1	c.804G>A	p.Glu268Glu	synonymous_variant	Exon 7 of 10		XP_047302295.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DRC1	ENST00000288710.7	c.1824G>A	p.Glu608Glu	synonymous_variant	Exon 14 of 17	2	NM_145038.5	ENSP00000288710.2
DRC1	ENST00000439066.2	n.554G>A		non_coding_transcript_exon_variant	Exon 5 of 5	3
DRC1	ENST00000649059.1	n.*787G>A		non_coding_transcript_exon_variant	Exon 13 of 16			ENSP00000497543.1
DRC1	ENST00000649059.1	n.*787G>A		3_prime_UTR_variant	Exon 13 of 16			ENSP00000497543.1

Frequencies

GnomAD3 genomes AF: 0.00522 AC: 794 AN: 152198 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.0175

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00670

GnomAD4 exome AF: 0.000566 AC: 828 AN: 1461830 Hom.: 5 Cov.: 31 AF XY: 0.000505 AC XY: 367 AN XY: 727206

African (AFR) AF: 0.0178 AC: 596 AN: 33476

American (AMR) AF: 0.00199 AC: 89 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

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

South Asian (SAS) AF: 0.0000696 AC: 6 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53390

Middle Eastern (MID) AF: 0.000867 AC: 5 AN: 5768

European-Non Finnish (NFE) AF: 0.0000441 AC: 49 AN: 1111992

Other (OTH) AF: 0.00137 AC: 83 AN: 60396

GnomAD4 genome AF: 0.00522 AC: 795 AN: 152316 Hom.: 4 Cov.: 33 AF XY: 0.00537 AC XY: 400 AN XY: 74482

African (AFR) AF: 0.0174 AC: 725 AN: 41568

American (AMR) AF: 0.00327 AC: 50 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68032

Other (OTH) AF: 0.00663 AC: 14 AN: 2112

Alfa AF: 0.00241 Hom.: 1

Bravo AF: 0.00598

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Primary ciliary dyskinesia Benign:1

Jan 23, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.19
PhyloP100		-0.90
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs1402962; hg19: chr2-26676322;