Genetic Variant NM_024093.3:c.477T>C (chr2-105343058-T-C) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

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

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.72

Publications

1 publications found

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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 link	c.477T>C	p.Pro159Pro	synonymous_variant	Exon 3 of 4	ENST00000258457.7	NP_076998.1	Q9BVC5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
C2orf49	ENST00000258457.7 link	c.477T>C	p.Pro159Pro	synonymous_variant	Exon 3 of 4	1	NM_024093.3	ENSP00000258457.2	Q9BVC5-1
C2orf49	ENST00000410049.1 link	c.394-43T>C		intron_variant	Intron 3 of 4	1		ENSP00000386361.1	C9J4K0
C2orf49	ENST00000718457.1 link	c.477T>C	p.Pro159Pro	synonymous_variant	Exon 3 of 5			ENSP00000520835.1

Frequencies

GnomAD3 genomes

AF:

0.00593

AC:

902

AN:

152212

Hom.:

Cov.:

show subpopulations

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

show subpopulations

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.:

Cov.:

AF XY:

0.00681

AC XY:

4952

AN XY:

727248

show subpopulations

African (AFR)

AF:

0.000896

AC:

AN:

33480

American (AMR)

AF:

0.00148

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00968

AC:

253

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

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:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00639

AC:

7102

AN:

1112012

Other (OTH)

AF:

0.00735

AC:

444

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

588

1175

1763

2350

2938

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00592

AC:

902

AN:

152330

Hom.:

Cov.:

AF XY:

0.00694

AC XY:

517

AN XY:

74494

show subpopulations

African (AFR)

AF:

0.000746

AC:

AN:

41570

American (AMR)

AF:

0.00131

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.0118

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5186

South Asian (SAS)

AF:

0.00352

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0355

AC:

377

AN:

10618

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00594

AC:

404

AN:

68030

Other (OTH)

AF:

0.00474

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

140

187

234

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00566

Hom.:

Bravo

AF:

0.00340

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00485

EpiControl

AF:

0.00539

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

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

(source)

DANN

Benign

0.78

PhyloP100

2.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

NM_024093.3:c.477T>C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over