2-105343058-T-C

Variant names:

• chr2-105343058-T-C
• rs138797707
• NM_024093.3:c.477T>C

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_024093.3(C2orf49):​c.477T>C​(p.Pro159Pro) 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
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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 GnomAd4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C2orf49	NM_024093.3	c.477T>C	p.Pro159Pro	synonymous_variant	Exon 3 of 4	ENST00000258457.7	NP_076998.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C2orf49	ENST00000258457.7	c.477T>C	p.Pro159Pro	synonymous_variant	Exon 3 of 4	1	NM_024093.3	ENSP00000258457.2
C2orf49	ENST00000410049.1	c.394-43T>C		intron_variant	Intron 3 of 4	1		ENSP00000386361.1
C2orf49	ENST00000718457.1	c.477T>C	p.Pro159Pro	synonymous_variant	Exon 3 of 5			ENSP00000520835.1

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

GnomAD2 exomes AF: 0.00717 AC: 1802 AN: 251436 AF XY: 0.00715

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 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

African (AFR) AF: 0.000896 AC: 30 AN: 33480

American (AMR) AF: 0.00148 AC: 66 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00968 AC: 253 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00374 AC: 323 AN: 86258

European-Finnish (FIN) AF: 0.0337 AC: 1802 AN: 53420

Middle Eastern (MID) AF: 0.00277 AC: 16 AN: 5768

European-Non Finnish (NFE) AF: 0.00639 AC: 7102 AN: 1112012

Other (OTH) AF: 0.00735 AC: 444 AN: 60396

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

African (AFR) AF: 0.000746 AC: 31 AN: 41570

American (AMR) AF: 0.00131 AC: 20 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0118 AC: 41 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.00352 AC: 17 AN: 4830

European-Finnish (FIN) AF: 0.0355 AC: 377 AN: 10618

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00594 AC: 404 AN: 68030

Other (OTH) AF: 0.00474 AC: 10 AN: 2110

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

Sep 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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
PhyloP100		2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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: rs138797707; hg19: chr2-105959515;