2-105337597-G-T

Variant names:

• chr2-105337597-G-T
• rs142827498
• NM_024093.3:c.10G>T

Variant summary

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

The NM_024093.3(C2orf49):​c.10G>T​(p.Asp4Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,613,196 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 0.000020 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: C2orf49 NM_024093.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.19

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C2orf49	NM_024093.3	c.10G>T	p.Asp4Tyr	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.10G>T	p.Asp4Tyr	missense_variant	Exon 1 of 4	1	NM_024093.3	ENSP00000258457.2
C2orf49	ENST00000410049.1	c.10G>T	p.Asp4Tyr	missense_variant	Exon 1 of 5	1		ENSP00000386361.1
C2orf49-DT	ENST00000610036.2	n.-88C>A		upstream_gene_variant		6

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152046 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

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 AF: 0.00000137 AC: 2 AN: 1461150 Hom.: 0 Cov.: 44 AF XY: 0.00000275 AC XY: 2 AN XY: 726902

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152046 Hom.: 0 Cov.: 30 AF XY: 0.0000404 AC XY: 3 AN XY: 74284

Gnomad4 AFR AF: 0.0000242

Gnomad4 AMR AF: 0.000131

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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.094	T
BayesDel_noAF	Benign	-0.37
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.016	T;T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.62	T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.1	L;.
PROVEAN	Uncertain	-2.4	N;N
REVEL	Benign	0.12
Sift	Uncertain	0.020	D;D
Sift4G	Uncertain	0.048	D;T
Polyphen		0.0	B;.
Vest4		0.18
MutPred		0.17		Loss of disorder (P = 0.053);Loss of disorder (P = 0.053);
MVP		0.59
MPC		0.030
ClinPred		0.32	T
GERP RS		2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.19
gMVP		0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.39		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.39		Position offset: -2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs142827498; hg19: chr2-105954054;