chr2-26456526-G-A

Variant names:

• chr2-26456526-G-A
• rs1054737
• NM_145038.5:c.*9G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_145038.5(DRC1):​c.*9G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0612 in 1,613,910 control chromosomes in the GnomAD database, including 3,534 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.046 (213 hom., cov: 33)
  • Exomes 𝑓: 0.063 (3321 hom.)
• Consequence: DRC1 NM_145038.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.830
• Publications: 5 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 2-26456526-G-A is Benign according to our data. Variant chr2-26456526-G-A is described in ClinVar as [Benign]. Clinvar id is 262563.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.064 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRC1	NM_145038.5	c.*9G>A		3_prime_UTR_variant	Exon 17 of 17	ENST00000288710.7	NP_659475.2
DRC1	XM_047446339.1	c.*9G>A		3_prime_UTR_variant	Exon 10 of 10		XP_047302295.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DRC1	ENST00000288710.7	c.*9G>A		3_prime_UTR_variant	Exon 17 of 17	2	NM_145038.5	ENSP00000288710.2
DRC1	ENST00000649059.1	n.*1195G>A		non_coding_transcript_exon_variant	Exon 16 of 16			ENSP00000497543.1
DRC1	ENST00000649059.1	n.*1195G>A		3_prime_UTR_variant	Exon 16 of 16			ENSP00000497543.1

Frequencies

GnomAD3 genomes AF: 0.0462 AC: 7038 AN: 152204 Hom.: 213 Cov.: 33

Gnomad AFR AF: 0.0320

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.0339

Gnomad ASJ AF: 0.0412

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0244

Gnomad FIN AF: 0.0312

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0657

Gnomad OTH AF: 0.0435

GnomAD2 exomes AF: 0.0436 AC: 10962 AN: 251272 AF XY: 0.0449

Gnomad AFR exome AF: 0.0321

Gnomad AMR exome AF: 0.0243

Gnomad ASJ exome AF: 0.0401

Gnomad EAS exome AF: 0.000381

Gnomad FIN exome AF: 0.0341

Gnomad NFE exome AF: 0.0651

Gnomad OTH exome AF: 0.0480

GnomAD4 exome AF: 0.0628 AC: 91745 AN: 1461590 Hom.: 3321 Cov.: 31 AF XY: 0.0613 AC XY: 44592 AN XY: 727086

African (AFR) AF: 0.0286 AC: 956 AN: 33474

American (AMR) AF: 0.0248 AC: 1110 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.0403 AC: 1053 AN: 26128

East Asian (EAS) AF: 0.00111 AC: 44 AN: 39696

South Asian (SAS) AF: 0.0254 AC: 2186 AN: 86226

European-Finnish (FIN) AF: 0.0375 AC: 2004 AN: 53420

Middle Eastern (MID) AF: 0.0300 AC: 173 AN: 5760

European-Non Finnish (NFE) AF: 0.0727 AC: 80814 AN: 1111794

Other (OTH) AF: 0.0564 AC: 3405 AN: 60390

GnomAD4 genome AF: 0.0462 AC: 7039 AN: 152320 Hom.: 213 Cov.: 33 AF XY: 0.0433 AC XY: 3223 AN XY: 74480

African (AFR) AF: 0.0320 AC: 1329 AN: 41580

American (AMR) AF: 0.0339 AC: 518 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0412 AC: 143 AN: 3470

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5190

South Asian (SAS) AF: 0.0244 AC: 118 AN: 4830

European-Finnish (FIN) AF: 0.0312 AC: 331 AN: 10620

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0656 AC: 4463 AN: 68012

Other (OTH) AF: 0.0435 AC: 92 AN: 2114

Alfa AF: 0.0563 Hom.: 533

Bravo AF: 0.0463

Asia WGS AF: 0.0140 AC: 53 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

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PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:2

Jul 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.43
DANN	Benign	0.93
PhyloP100		-0.83
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1054737; hg19: chr2-26679394;