Variant rs2267163 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.754-31T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.562 in 1,613,238 control chromosomes in the GnomAD database, including 258,768 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.62 ( 29845 hom., cov: 32)

Exomes 𝑓: 0.56 ( 228923 hom. )

Consequence

TCN2
NM_000355.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.272

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:

TCN2 (HGNC:):

TCN2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

This place is a probable branch point but likely benign (scored 0 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 22-30615570-T-C is Benign according to our data. Variant chr22-30615570-T-C is described in ClinVar as [Benign]. Clinvar id is 1236541.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.751 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.754-31T>C		intron_variant		ENST00000215838.8	NP_000346.2	P20062-1
TCN2	NM_001184726.2 linkuse as main transcript	c.673-31T>C		intron_variant			NP_001171655.1	P20062-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCN2	ENST00000215838.8 linkuse as main transcript	c.754-31T>C		intron_variant		1	NM_000355.4	ENSP00000215838.3		P20062-1

Frequencies

GnomAD3 genomes

AF:

0.619

AC:

94080

AN:

151878

Hom.:

29815

Cov.:

show subpopulations

Gnomad AFR

AF:

0.759

Gnomad AMI

AF:

0.575

Gnomad AMR

AF:

0.647

Gnomad ASJ

AF:

0.583

Gnomad EAS

AF:

0.441

Gnomad SAS

AF:

0.408

Gnomad FIN

AF:

0.633

Gnomad MID

AF:

0.541

Gnomad NFE

AF:

0.558

Gnomad OTH

AF:

0.604

GnomAD3 exomes

AF:

0.569

AC:

142218

AN:

249820

Hom.:

41744

AF XY:

0.559

AC XY:

75496

AN XY:

135148

show subpopulations

Gnomad AFR exome

AF:

0.763

Gnomad AMR exome

AF:

0.667

Gnomad ASJ exome

AF:

0.591

Gnomad EAS exome

AF:

0.428

Gnomad SAS exome

AF:

0.414

Gnomad FIN exome

AF:

0.635

Gnomad NFE exome

AF:

0.562

Gnomad OTH exome

AF:

0.578

GnomAD4 exome

AF:

0.556

AC:

811838

AN:

1461242

Hom.:

228923

Cov.:

AF XY:

0.551

AC XY:

400763

AN XY:

726854

show subpopulations

Gnomad4 AFR exome

AF:

0.779

Gnomad4 AMR exome

AF:

0.663

Gnomad4 ASJ exome

AF:

0.586

Gnomad4 EAS exome

AF:

0.445

Gnomad4 SAS exome

AF:

0.419

Gnomad4 FIN exome

AF:

0.635

Gnomad4 NFE exome

AF:

0.554

Gnomad4 OTH exome

AF:

0.567

GnomAD4 genome

AF:

0.619

AC:

94161

AN:

151996

Hom.:

29845

Cov.:

AF XY:

0.618

AC XY:

45880

AN XY:

74266

show subpopulations

Gnomad4 AFR

AF:

0.758

Gnomad4 AMR

AF:

0.647

Gnomad4 ASJ

AF:

0.583

Gnomad4 EAS

AF:

0.441

Gnomad4 SAS

AF:

0.407

Gnomad4 FIN

AF:

0.633

Gnomad4 NFE

AF:

0.559

Gnomad4 OTH

AF:

0.598

Alfa

AF:

0.578

Hom.:

26343

Bravo

AF:

0.628

Asia WGS

AF:

0.467

AC:

1627

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	clinical testing	GeneDx	Jul 15, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Transcobalamin II deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

3.0

DANN

Benign

0.70

BranchPoint Hunter

0.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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