12-48914692-G-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_033124.5(DRC2):​c.470+119G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 719,104 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: DRC2 NM_033124.5 intron
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000139 AC: 1 AN: 719104 Hom.: 0 AF XY: 0.00000275 AC XY: 1 AN XY: 364002

African (AFR) AF: 0.00 AC: 0 AN: 17972

American (AMR) AF: 0.00 AC: 0 AN: 19334

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14852

East Asian (EAS) AF: 0.00 AC: 0 AN: 31890

South Asian (SAS) AF: 0.0000209 AC: 1 AN: 47802

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2442

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 511154

Other (OTH) AF: 0.00 AC: 0 AN: 34264

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.24
DANN	Benign	0.71
PhyloP100		-0.30

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;