rs2301955

chr22-30622659-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000355.4(TCN2):c.1107-309C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 151,984 control chromosomes in the GnomAD database, including 10,073 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.35 (10073 hom., cov: 32)
• Consequence: TCN2 NM_000355.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.22

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 22-30622659-C-T is Benign according to our data. Variant chr22-30622659-C-T is described in ClinVar as [Benign]. Clinvar id is 1227845.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TCN2	NM_000355.4	c.1107-309C>T		intron_variant		ENST00000215838.8
TCN2	NM_001184726.2	c.1026-309C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TCN2	ENST00000215838.8	c.1107-309C>T		intron_variant		1	NM_000355.4	P2

Frequencies

GnomAD3 genomes AF: 0.355 AC: 53940 AN: 151864 Hom.: 10071 Cov.: 32

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.447

Gnomad EAS AF: 0.194

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.449

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.419

Gnomad OTH AF: 0.370

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.355 AC: 53945 AN: 151984 Hom.: 10073 Cov.: 32 AF XY: 0.353 AC XY: 26232 AN XY: 74292

Gnomad4 AFR AF: 0.251

Gnomad4 AMR AF: 0.343

Gnomad4 ASJ AF: 0.447

Gnomad4 EAS AF: 0.194

Gnomad4 SAS AF: 0.266

Gnomad4 FIN AF: 0.449

Gnomad4 NFE AF: 0.419

Gnomad4 OTH AF: 0.365

Alfa AF: 0.399 Hom.: 5780

Bravo AF: 0.343

Asia WGS AF: 0.262 AC: 914 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 15, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.61
Dann	Benign	0.40

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

Other links and lift over

dbSNP: rs2301955; hg19: chr22-31018646;