rs10875894

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_033124.5(DRC2):c.1176C>A(p.Thr392Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 1,609,902 control chromosomes in the GnomAD database, including 114,947 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.33 ( 9119 hom., cov: 31)

Exomes 𝑓: 0.37 ( 105828 hom. )

Consequence

DRC2
NM_033124.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.0960

Publications

23 publications found

Variant links:

Genes affected

DRC2 (HGNC:29937): (coiled-coil domain containing 65) This gene encodes a sperm tail protein that is highly expressed in adult testis, spermatocytes and spermatids. The protein plays a critical role in the assembly of the nexin-dynein regulatory complex. Mutations in this gene result in primary ciliary dyskinesia. [provided by RefSeq, Nov 2013]

DRC2 Gene-Disease associations (from GenCC):

primary ciliary dyskinesia 27
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P
primary ciliary dyskinesia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

DRC2 links:

ENSG00000272822 (HGNC:):

ENSG00000272822 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 12-48921079-C-A is Benign according to our data. Variant chr12-48921079-C-A is described in ClinVar as Benign. ClinVar VariationId is 402503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.096 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRC2	NM_033124.5 link	c.1176C>A	p.Thr392Thr	synonymous_variant	Exon 7 of 8	ENST00000320516.5	NP_149115.2
DRC2	NM_001286957.2 link	c.747C>A	p.Thr249Thr	synonymous_variant	Exon 7 of 8		NP_001273886.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC65	ENST00000320516.5 link	c.1176C>A	p.Thr392Thr	synonymous_variant	Exon 7 of 8	1	NM_033124.5	ENSP00000312706.4
ENSG00000272822	ENST00000398092.4 link	c.385-17171G>T		intron_variant	Intron 4 of 4	3		ENSP00000438507.1

Frequencies

GnomAD3 genomes

AF:

0.326

AC:

49549

AN:

151890

Hom.:

9111

Cov.:

show subpopulations

Gnomad AFR

AF:

0.157

Gnomad AMI

AF:

0.434

Gnomad AMR

AF:

0.474

Gnomad ASJ

AF:

0.435

Gnomad EAS

AF:

0.467

Gnomad SAS

AF:

0.222

Gnomad FIN

AF:

0.373

Gnomad MID

AF:

0.399

Gnomad NFE

AF:

0.377

Gnomad OTH

AF:

0.357

GnomAD2 exomes

AF:

0.382

AC:

95332

AN:

249870

AF XY:

0.373

show subpopulations

Gnomad AFR exome

AF:

0.149

Gnomad AMR exome

AF:

0.552

Gnomad ASJ exome

AF:

0.437

Gnomad EAS exome

AF:

0.466

Gnomad FIN exome

AF:

0.383

Gnomad NFE exome

AF:

0.387

Gnomad OTH exome

AF:

0.389

GnomAD4 exome

AF:

0.375

AC:

546543

AN:

1457894

Hom.:

105828

Cov.:

AF XY:

0.371

AC XY:

269081

AN XY:

724668

show subpopulations

African (AFR)

AF:

0.150

AC:

5002

AN:

33260

American (AMR)

AF:

0.538

AC:

23849

AN:

44308

Ashkenazi Jewish (ASJ)

AF:

0.431

AC:

11223

AN:

26012

East Asian (EAS)

AF:

0.475

AC:

18820

AN:

39608

South Asian (SAS)

AF:

0.224

AC:

19280

AN:

86098

European-Finnish (FIN)

AF:

0.387

AC:

20623

AN:

53306

Middle Eastern (MID)

AF:

0.377

AC:

2162

AN:

5742

European-Non Finnish (NFE)

AF:

0.382

AC:

423565

AN:

1109398

Other (OTH)

AF:

0.366

AC:

22019

AN:

60162

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

18185

36370

54555

72740

90925

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13226

26452

39678

52904

66130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.326

AC:

49568

AN:

152008

Hom.:

9119

Cov.:

AF XY:

0.330

AC XY:

24508

AN XY:

74296

show subpopulations

African (AFR)

AF:

0.157

AC:

6500

AN:

41476

American (AMR)

AF:

0.475

AC:

7249

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.435

AC:

1508

AN:

3468

East Asian (EAS)

AF:

0.467

AC:

2412

AN:

5162

South Asian (SAS)

AF:

0.221

AC:

1064

AN:

4820

European-Finnish (FIN)

AF:

0.373

AC:

3939

AN:

10550

Middle Eastern (MID)

AF:

0.398

AC:

117

AN:

294

European-Non Finnish (NFE)

AF:

0.377

AC:

25625

AN:

67944

Other (OTH)

AF:

0.360

AC:

759

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1636

3272

4908

6544

8180

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

480

960

1440

1920

2400

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.375

Hom.:

17753

Bravo

AF:

0.337

Asia WGS

AF:

0.358

AC:

1242

AN:

3478

EpiCase

AF:

0.389

EpiControl

AF:

0.392

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia 27

Benign:2

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Nov 10, 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

- -

not specified

Benign:1

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 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.78

(source)

DANN

Benign

0.68

PhyloP100

0.096

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over