Variant rs2072195 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.*225A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0692 in 613,678 control chromosomes in the GnomAD database, including 4,745 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 2563 hom., cov: 33)

Exomes 𝑓: 0.052 ( 2182 hom. )

Consequence

TCN2
NM_000355.4 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.917

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=-0.84).

BP6

Variant 22-30626746-A-T is Benign according to our data. Variant chr22-30626746-A-T is described in ClinVar as [Benign]. Clinvar id is 341221.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCN2	NM_000355.4 link	c.*225A>T		3_prime_UTR_variant	9/9	ENST00000215838.8	NP_000346.2	P20062-1
TCN2	NM_001184726.2 link	c.*225A>T		3_prime_UTR_variant	9/9		NP_001171655.1	P20062-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCN2	ENST00000215838.8 link	c.*225A>T		3_prime_UTR_variant	9/9	1	NM_000355.4	ENSP00000215838.3		P20062-1

Frequencies

GnomAD3 genomes

AF:

0.121

AC:

18474

AN:

152162

Hom.:

2553

Cov.:

show subpopulations

Gnomad AFR

AF:

0.324

Gnomad AMI

AF:

0.0241

Gnomad AMR

AF:

0.137

Gnomad ASJ

AF:

0.0280

Gnomad EAS

AF:

0.249

Gnomad SAS

AF:

0.0358

Gnomad FIN

AF:

0.0220

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0142

Gnomad OTH

AF:

0.0932

GnomAD4 exome

AF:

0.0519

AC:

23942

AN:

461396

Hom.:

2182

Cov.:

AF XY:

0.0489

AC XY:

11877

AN XY:

243008

show subpopulations

Gnomad4 AFR exome

AF:

0.313

Gnomad4 AMR exome

AF:

0.173

Gnomad4 ASJ exome

AF:

0.0252

Gnomad4 EAS exome

AF:

0.251

Gnomad4 SAS exome

AF:

0.0359

Gnomad4 FIN exome

AF:

0.0197

Gnomad4 NFE exome

AF:

0.0139

Gnomad4 OTH exome

AF:

0.0603

GnomAD4 genome

AF:

0.122

AC:

18515

AN:

152282

Hom.:

2563

Cov.:

AF XY:

0.121

AC XY:

9018

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.324

Gnomad4 AMR

AF:

0.137

Gnomad4 ASJ

AF:

0.0280

Gnomad4 EAS

AF:

0.249

Gnomad4 SAS

AF:

0.0354

Gnomad4 FIN

AF:

0.0220

Gnomad4 NFE

AF:

0.0141

Gnomad4 OTH

AF:

0.0926

Alfa

AF:

0.0688

Hom.:

171

Bravo

AF:

0.142

Asia WGS

AF:

0.137

AC:

479

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 31, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Transcobalamin II deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.69

DANN

Benign

0.40

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