12-48914692-G-A

Variant names:

• chr12-48914692-G-A
• rs10783293
• NM_033124.5:c.470+119G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.297
• Publications: 10 publications found

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

ENSG00000272822 (HGNC:):

ACMG classification

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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033124.5. 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
	DRC2	NM_033124.5	MANE Select	c.470+119G>A		intron	N/A	NP_149115.2
	DRC2	NM_001286957.2		c.41+119G>A		intron	N/A	NP_001273886.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC65	ENST00000320516.5	TSL:1 MANE Select	c.470+119G>A		intron	N/A	ENSP00000312706.4
	ENSG00000272822	ENST00000398092.4	TSL:3	c.385-10784C>T		intron	N/A	ENSP00000438507.1
	CCDC65	ENST00000266984.9	TSL:5	c.470+119G>A		intron	N/A	ENSP00000266984.5

Frequencies

GnomAD3 genomes AF: 0.395 AC: 59933 AN: 151780 Hom.: 12616 Cov.: 31

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

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

GnomAD4 genome AF: 0.395 AC: 59961 AN: 151896 Hom.: 12624 Cov.: 31 AF XY: 0.398 AC XY: 29563 AN XY: 74220

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

Alfa AF: 0.437 Hom.: 19453

Bravo AF: 0.400

Asia WGS AF: 0.370 AC: 1286 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.58
DANN	Benign	0.70
PhyloP100		-0.30
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: rs10783293; hg19: chr12-49308475; COSMIC: COSV57194486; COSMIC: COSV57194486;