rs144573949

Variant names:

• chr12-48918325-A-C
• rs144573949
• NM_033124.5:c.660A>C

Your query was ambiguous. Multiple possible variants found:

• chr12-48918325-A-C
• chr12-48918325-A-G
• chr12-48918325-A-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_033124.5(DRC2):​c.660A>C​(p.Glu220Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. E220E) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DRC2 NM_033124.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.476
• Publications: 1 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24020278).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRC2	NM_033124.5	c.660A>C	p.Glu220Asp	missense_variant	Exon 5 of 8	ENST00000320516.5	NP_149115.2
DRC2	NM_001286957.2	c.231A>C	p.Glu77Asp	missense_variant	Exon 5 of 8		NP_001273886.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC65	ENST00000320516.5	c.660A>C	p.Glu220Asp	missense_variant	Exon 5 of 8	1	NM_033124.5	ENSP00000312706.4
ENSG00000272822	ENST00000398092.4	c.385-14417T>G		intron_variant	Intron 4 of 4	3		ENSP00000438507.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00000943 Hom.: 0

Bravo AF: 0.0000189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.064	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.019	.;.;T
Eigen	Benign	0.13
Eigen_PC	Benign	0.13
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.78	T;T;T
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.24	T;T;T
MetaSVM	Benign	-0.96	T
PhyloP100		0.48
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-2.1	N;N;N
REVEL	Benign	0.17
Sift	Benign	0.072	T;T;T
Sift4G	Benign	0.072	T;T;T
Polyphen		0.86	.;.;P
Vest4		0.39
MVP		0.014
MPC		0.18
ClinPred		0.94	D
GERP RS		4.2
Varity_R		0.27
gMVP		0.29
Mutation Taster		=50/50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs144573949; hg19: chr12-49312108;