chr12-48914559-G-A

Variant names:

• chr12-48914559-G-A
• rs145100370
• NM_033124.5:c.456G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP6_Very_Strong BP7

The NM_033124.5(DRC2):​c.456G>A​(p.Glu152Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000667 in 1,614,018 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00062 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00067 (1 hom.)
• Consequence: DRC2 NM_033124.5 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.06
• Publications: 0 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 12-48914559-G-A is Benign according to our data. Variant chr12-48914559-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 416604.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.06 with no splicing effect.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRC2	NM_033124.5	MANE Select	c.456G>A	p.Glu152Glu	synonymous	Exon 3 of 8	NP_149115.2
	DRC2	NM_001286957.2		c.27G>A	p.Glu9Glu	synonymous	Exon 3 of 8	NP_001273886.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC65	ENST00000320516.5	TSL:1 MANE Select	c.456G>A	p.Glu152Glu	synonymous	Exon 3 of 8	ENSP00000312706.4
	ENSG00000272822	ENST00000398092.4	TSL:3	c.385-10651C>T		intron	N/A	ENSP00000438507.1
	CCDC65	ENST00000266984.9	TSL:5	c.456G>A	p.Glu152Glu	synonymous	Exon 3 of 9	ENSP00000266984.5

Frequencies

GnomAD3 genomes AF: 0.000624 AC: 95 AN: 152206 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000982

Gnomad ASJ AF: 0.00577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000735

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.000805 AC: 202 AN: 251052 AF XY: 0.000810

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.000464

Gnomad ASJ exome AF: 0.00537

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.00103

Gnomad OTH exome AF: 0.000490

GnomAD4 exome AF: 0.000671 AC: 981 AN: 1461694 Hom.: 1 Cov.: 32 AF XY: 0.000644 AC XY: 468 AN XY: 727170

African (AFR) AF: 0.000149 AC: 5 AN: 33478

American (AMR) AF: 0.000403 AC: 18 AN: 44660

Ashkenazi Jewish (ASJ) AF: 0.00471 AC: 123 AN: 26126

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.000232 AC: 20 AN: 86242

European-Finnish (FIN) AF: 0.0000562 AC: 3 AN: 53404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.000683 AC: 759 AN: 1111926

Other (OTH) AF: 0.000861 AC: 52 AN: 60394

GnomAD4 genome AF: 0.000624 AC: 95 AN: 152324 Hom.: 1 Cov.: 32 AF XY: 0.000604 AC XY: 45 AN XY: 74482

African (AFR) AF: 0.000120 AC: 5 AN: 41578

American (AMR) AF: 0.000981 AC: 15 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00577 AC: 20 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10626

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000735 AC: 50 AN: 68018

Other (OTH) AF: 0.00142 AC: 3 AN: 2116

Alfa AF: 0.000819 Hom.: 0

Bravo AF: 0.000604

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00153

EpiControl AF: 0.00101

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Primary ciliary dyskinesia 27 Benign:2

May 16, 2022

Fulgent Genetics, Fulgent Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	9.3
DANN	Benign	0.76
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism

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: rs145100370; hg19: chr12-49308342;