2-105343058-T-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_024093.3(C2orf49):c.477T>C(p.Pro159=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00678 in 1,614,224 control chromosomes in the GnomAD database, including 68 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0059 (12 hom., cov: 33)
  • Exomes 𝑓: 0.0069 (56 hom.)
• Consequence: C2orf49 NM_024093.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.72

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]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 2-105343058-T-C is Benign according to our data. Variant chr2-105343058-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2651229.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.72 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C2orf49	NM_024093.3	c.477T>C	p.Pro159=	synonymous_variant	3/4	ENST00000258457.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C2orf49	ENST00000258457.7	c.477T>C	p.Pro159=	synonymous_variant	3/4	1	NM_024093.3	P1
C2orf49	ENST00000410049.1	c.394-43T>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.00593 AC: 902 AN: 152212 Hom.: 12 Cov.: 33

Gnomad AFR AF: 0.000748

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00131

Gnomad ASJ AF: 0.0118

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00331

Gnomad FIN AF: 0.0355

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00594

Gnomad OTH AF: 0.00479

GnomAD3 exomes AF: 0.00717 AC: 1802 AN: 251436 Hom.: 21 AF XY: 0.00715 AC XY: 972 AN XY: 135898

Gnomad AFR exome AF: 0.00129

Gnomad AMR exome AF: 0.00145

Gnomad ASJ exome AF: 0.00933

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00395

Gnomad FIN exome AF: 0.0344

Gnomad NFE exome AF: 0.00637

Gnomad OTH exome AF: 0.00765

GnomAD4 exome AF: 0.00687 AC: 10037 AN: 1461894 Hom.: 56 Cov.: 31 AF XY: 0.00681 AC XY: 4952 AN XY: 727248

Gnomad4 AFR exome AF: 0.000896

Gnomad4 AMR exome AF: 0.00148

Gnomad4 ASJ exome AF: 0.00968

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00374

Gnomad4 FIN exome AF: 0.0337

Gnomad4 NFE exome AF: 0.00639

Gnomad4 OTH exome AF: 0.00735

GnomAD4 genome AF: 0.00592 AC: 902 AN: 152330 Hom.: 12 Cov.: 33 AF XY: 0.00694 AC XY: 517 AN XY: 74494

Gnomad4 AFR AF: 0.000746

Gnomad4 AMR AF: 0.00131

Gnomad4 ASJ AF: 0.0118

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00352

Gnomad4 FIN AF: 0.0355

Gnomad4 NFE AF: 0.00594

Gnomad4 OTH AF: 0.00474

Alfa AF: 0.00566 Hom.: 0

Bravo AF: 0.00340

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00485

EpiControl AF: 0.00539

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2022

C2orf49: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
Cadd	Benign	12
Dann	Benign	0.78
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs138797707; hg19: chr2-105959515;