Genetic Variant DRC2:c.470+119G>A (chr12-48914692-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_033124.5(DRC2):c.470+119G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 867,758 control chromosomes in the GnomAD database, including 76,088 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.39 ( 12624 hom., cov: 31)

Exomes 𝑓: 0.41 ( 63464 hom. )

Consequence

DRC2
NM_033124.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.297

Publications

10 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BP6

Variant 12-48914692-G-A is Benign according to our data. Variant chr12-48914692-G-A is described in ClinVar as [Benign]. Clinvar id is 1250781.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.51 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRC2	NM_033124.5 link	c.470+119G>A		intron_variant	Intron 3 of 7	ENST00000320516.5	NP_149115.2	Q8IXS2-1
DRC2	NM_001286957.2 link	c.41+119G>A		intron_variant	Intron 3 of 7		NP_001273886.1	B4DXQ7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC65	ENST00000320516.5 link	c.470+119G>A		intron_variant	Intron 3 of 7	1	NM_033124.5	ENSP00000312706.4		Q8IXS2-1
ENSG00000272822	ENST00000398092.4 link	c.385-10784C>T		intron_variant	Intron 4 of 4	3		ENSP00000438507.1		F5H423

Frequencies

GnomAD3 genomes

AF:

0.395

AC:

59933

AN:

151780

Hom.:

12616

Cov.:

show subpopulations

Gnomad AFR

AF:

0.256

Gnomad AMI

AF:

0.490

Gnomad AMR

AF:

0.519

Gnomad ASJ

AF:

0.453

Gnomad EAS

AF:

0.468

Gnomad SAS

AF:

0.232

Gnomad FIN

AF:

0.483

Gnomad MID

AF:

0.408

Gnomad NFE

AF:

0.439

Gnomad OTH

AF:

0.417

GnomAD4 exome

AF:

0.413

AC:

295633

AN:

715862

Hom.:

63464

AF XY:

0.407

AC XY:

147545

AN XY:

362412

show subpopulations

African (AFR)

AF:

0.246

AC:

4416

AN:

17922

American (AMR)

AF:

0.528

AC:

10156

AN:

19234

Ashkenazi Jewish (ASJ)

AF:

0.435

AC:

6440

AN:

14810

East Asian (EAS)

AF:

0.469

AC:

14913

AN:

31796

South Asian (SAS)

AF:

0.217

AC:

10301

AN:

47548

European-Finnish (FIN)

AF:

0.482

AC:

18927

AN:

39256

Middle Eastern (MID)

AF:

0.384

AC:

932

AN:

2426

European-Non Finnish (NFE)

AF:

0.424

AC:

215663

AN:

508768

Other (OTH)

AF:

0.407

AC:

13885

AN:

34102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

7807

15613

23420

31226

39033

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.395

AC:

59961

AN:

151896

Hom.:

12624

Cov.:

AF XY:

0.398

AC XY:

29563

AN XY:

74220

show subpopulations

African (AFR)

AF:

0.256

AC:

10598

AN:

41422

American (AMR)

AF:

0.520

AC:

7929

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.453

AC:

1572

AN:

3470

East Asian (EAS)

AF:

0.468

AC:

2412

AN:

5156

South Asian (SAS)

AF:

0.230

AC:

1108

AN:

4810

European-Finnish (FIN)

AF:

0.483

AC:

5085

AN:

10538

Middle Eastern (MID)

AF:

0.408

AC:

120

AN:

294

European-Non Finnish (NFE)

AF:

0.439

AC:

29807

AN:

67926

Other (OTH)

AF:

0.419

AC:

885

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1790

3580

5370

7160

8950

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.437

Hom.:

19453

Bravo

AF:

0.400

Asia WGS

AF:

0.370

AC:

1286

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 10, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.58

(source)

DANN

Benign

0.70

PhyloP100

-0.30

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

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12-48914692-G-A

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