chr12-48918810-A-G

Variant names:

• chr12-48918810-A-G
• rs10875893
• NM_033124.5:c.933A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_033124.5(DRC2):​c.933A>G​(p.Arg311Arg) 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 1,613,438 control chromosomes in the GnomAD database, including 115,390 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.33 (9126 hom., cov: 31)
  • Exomes 𝑓: 0.38 (106264 hom.)
• Consequence: DRC2 NM_033124.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 2.12
• Publications: 22 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: G2P, Labcorp Genetics (formerly Invitae), ClinGen
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000272822 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 12-48918810-A-G is Benign according to our data. Variant chr12-48918810-A-G is described in ClinVar as Benign. ClinVar VariationId is 402502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.12 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.466 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.933A>G	p.Arg311Arg	synonymous	Exon 6 of 8	NP_149115.2	Q8IXS2-1
	DRC2	NM_001286957.2		c.504A>G	p.Arg168Arg	synonymous	Exon 6 of 8	NP_001273886.1	B4DXQ7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC65	ENST00000320516.5	TSL:1 MANE Select	c.933A>G	p.Arg311Arg	synonymous	Exon 6 of 8	ENSP00000312706.4	Q8IXS2-1
	ENSG00000272822	ENST00000398092.4	TSL:3	c.385-14902T>C		intron	N/A	ENSP00000438507.1	F5H423
	CCDC65	ENST00000266984.9	TSL:5	c.933A>G	p.Arg311Arg	synonymous	Exon 6 of 9	ENSP00000266984.5	Q8IXS2-2

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49575 AN: 151930 Hom.: 9118 Cov.: 31

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.474

Gnomad ASJ AF: 0.437

Gnomad EAS AF: 0.465

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.377

Gnomad OTH AF: 0.358

GnomAD2 exomes AF: 0.382 AC: 96027 AN: 251420 AF XY: 0.374

Gnomad AFR exome AF: 0.150

Gnomad AMR exome AF: 0.553

Gnomad ASJ exome AF: 0.440

Gnomad EAS exome AF: 0.464

Gnomad FIN exome AF: 0.383

Gnomad NFE exome AF: 0.388

Gnomad OTH exome AF: 0.390

GnomAD4 exome AF: 0.375 AC: 548159 AN: 1461390 Hom.: 106264 Cov.: 39 AF XY: 0.372 AC XY: 270132 AN XY: 727022

African (AFR) AF: 0.151 AC: 5054 AN: 33478

American (AMR) AF: 0.539 AC: 24094 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.435 AC: 11363 AN: 26128

East Asian (EAS) AF: 0.474 AC: 18807 AN: 39696

South Asian (SAS) AF: 0.224 AC: 19315 AN: 86250

European-Finnish (FIN) AF: 0.387 AC: 20657 AN: 53420

Middle Eastern (MID) AF: 0.378 AC: 2182 AN: 5768

European-Non Finnish (NFE) AF: 0.382 AC: 424557 AN: 1111548

Other (OTH) AF: 0.366 AC: 22130 AN: 60386

GnomAD4 genome AF: 0.326 AC: 49594 AN: 152048 Hom.: 9126 Cov.: 31 AF XY: 0.330 AC XY: 24502 AN XY: 74316

African (AFR) AF: 0.157 AC: 6509 AN: 41468

American (AMR) AF: 0.475 AC: 7262 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.437 AC: 1516 AN: 3470

East Asian (EAS) AF: 0.465 AC: 2398 AN: 5154

South Asian (SAS) AF: 0.221 AC: 1066 AN: 4826

European-Finnish (FIN) AF: 0.372 AC: 3929 AN: 10568

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.377 AC: 25640 AN: 67960

Other (OTH) AF: 0.361 AC: 761 AN: 2108

Alfa AF: 0.366 Hom.: 8995

Bravo AF: 0.337

Asia WGS AF: 0.358 AC: 1243 AN: 3478

EpiCase AF: 0.390

EpiControl AF: 0.392

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	Primary ciliary dyskinesia 27 (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	8.4
DANN	Benign	0.65
PhyloP100		2.1
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: rs10875893; hg19: chr12-49312593; COSMIC: COSV56739264; COSMIC: COSV56739264;