Variant rs2283873 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000355.4(TCN2):c.941-21G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0495 in 1,613,756 control chromosomes in the GnomAD database, including 6,861 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 2288 hom., cov: 31)

Exomes 𝑓: 0.042 ( 4573 hom. )

Consequence

TCN2
NM_000355.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.274

Variant links:

Genes affected

TCN2 (HGNC:11653): (transcobalamin 2) This gene encodes a member of the vitamin B12-binding protein family. This family of proteins, alternatively referred to as R binders, is expressed in various tissues and secretions. This plasma protein binds cobalamin and mediates the transport of cobalamin into cells. This protein and other mammalian cobalamin-binding proteins, such as transcobalamin I and gastric intrisic factor, may have evolved by duplication of a common ancestral gene. Alternative splicing results in multiple transcript variants.[provided by RefSeq, May 2010]

TCN2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 22-30617309-G-A is Benign according to our data. Variant chr22-30617309-G-A is described in ClinVar as [Benign]. Clinvar id is 1222428.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.298 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCN2	NM_000355.4 linkuse as main transcript	c.941-21G>A		intron_variant		ENST00000215838.8	NP_000346.2
TCN2	NM_001184726.2 linkuse as main transcript	c.860-21G>A		intron_variant			NP_001171655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCN2	ENST00000215838.8 linkuse as main transcript	c.941-21G>A		intron_variant		1	NM_000355.4	ENSP00000215838	P2	P20062-1

Frequencies

GnomAD3 genomes

AF:

0.119

AC:

18115

AN:

151992

Hom.:

2280

Cov.:

show subpopulations

Gnomad AFR

AF:

0.303

Gnomad AMI

AF:

0.0297

Gnomad AMR

AF:

0.134

Gnomad ASJ

AF:

0.0311

Gnomad EAS

AF:

0.244

Gnomad SAS

AF:

0.0600

Gnomad FIN

AF:

0.0267

Gnomad MID

AF:

0.0414

Gnomad NFE

AF:

0.0204

Gnomad OTH

AF:

0.0914

GnomAD3 exomes

AF:

0.0882

AC:

22156

AN:

251262

Hom.:

2259

AF XY:

0.0773

AC XY:

10493

AN XY:

135812

show subpopulations

Gnomad AFR exome

AF:

0.309

Gnomad AMR exome

AF:

0.208

Gnomad ASJ exome

AF:

0.0260

Gnomad EAS exome

AF:

0.239

Gnomad SAS exome

AF:

0.0657

Gnomad FIN exome

AF:

0.0274

Gnomad NFE exome

AF:

0.0208

Gnomad OTH exome

AF:

0.0520

GnomAD4 exome

AF:

0.0423

AC:

61776

AN:

1461646

Hom.:

4573

Cov.:

AF XY:

0.0415

AC XY:

30162

AN XY:

727136

show subpopulations

Gnomad4 AFR exome

AF:

0.316

Gnomad4 AMR exome

AF:

0.195

Gnomad4 ASJ exome

AF:

0.0286

Gnomad4 EAS exome

AF:

0.248

Gnomad4 SAS exome

AF:

0.0666

Gnomad4 FIN exome

AF:

0.0248

Gnomad4 NFE exome

AF:

0.0188

Gnomad4 OTH exome

AF:

0.0589

GnomAD4 genome

AF:

0.119

AC:

18160

AN:

152110

Hom.:

2288

Cov.:

AF XY:

0.119

AC XY:

8868

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.303

Gnomad4 AMR

AF:

0.134

Gnomad4 ASJ

AF:

0.0311

Gnomad4 EAS

AF:

0.245

Gnomad4 SAS

AF:

0.0598

Gnomad4 FIN

AF:

0.0267

Gnomad4 NFE

AF:

0.0204

Gnomad4 OTH

AF:

0.0914

Alfa

AF:

0.0423

Hom.:

594

Bravo

AF:

0.138

Asia WGS

AF:

0.150

AC:

524

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 31, 2018	- -

Transcobalamin II deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 24, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

5.1

DANN

Benign

0.92

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over