rs991080602

Variant names:

• chr2-105337669-C-G
• rs991080602
• NM_024093.3:c.82C>G

Your query was ambiguous. Multiple possible variants found:

• chr2-105337669-C-G
• chr2-105337669-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024093.3(C2orf49):​c.82C>G​(p.Leu28Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000704 in 141,960 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: 𝑓 0.0000070 (0 hom., cov: 28)
• Consequence: C2orf49 NM_024093.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.58

Genes affected

C2orf49 (HGNC:28772): (chromosome 2 open reading frame 49) Predicted to be involved in embryonic morphogenesis. Located in nucleus. Part of tRNA-splicing ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

C2orf49-DT (HGNC:55178): (C2orf49 divergent transcript)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2634575).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C2orf49	NM_024093.3	c.82C>G	p.Leu28Val	missense_variant	Exon 1 of 4	ENST00000258457.7	NP_076998.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C2orf49	ENST00000258457.7	c.82C>G	p.Leu28Val	missense_variant	Exon 1 of 4	1	NM_024093.3	ENSP00000258457.2
C2orf49	ENST00000410049.1	c.82C>G	p.Leu28Val	missense_variant	Exon 1 of 5	1		ENSP00000386361.1
C2orf49-DT	ENST00000610036.2	n.-160G>C		upstream_gene_variant		6

Frequencies

GnomAD3 genomes AF: 0.00000704 AC: 1 AN: 141960 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000714

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 44

GnomAD4 genome AF: 0.00000704 AC: 1 AN: 141960 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 68730

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000714

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.082	T
BayesDel_noAF	Benign	-0.36
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.022	T;T
Eigen	Benign	0.18
Eigen_PC	Benign	0.18
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.84	T;T
M_CAP	Uncertain	0.087	D
MetaRNN	Benign	0.26	T;T
MetaSVM	Benign	-0.75	T
MutationAssessor	Uncertain	2.3	M;.
PROVEAN	Benign	-1.4	N;N
REVEL	Benign	0.095
Sift	Benign	0.053	T;T
Sift4G	Benign	0.10	T;T
Polyphen		0.91	P;.
Vest4		0.39
MutPred		0.28		Gain of relative solvent accessibility (P = 0.09);Gain of relative solvent accessibility (P = 0.09);
MVP		0.38
MPC		0.20
ClinPred		0.96	D
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.47
gMVP		0.16

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

Publications

LitVar

Other links and lift over

dbSNP: rs991080602; hg19: chr2-105954126;