Variant 2-46902145-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The ENST00000319466.9(MCFD2):c.*3318T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0587 in 152,726 control chromosomes in the GnomAD database, including 455 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.059 ( 455 hom., cov: 33)

Exomes 𝑓: 0.025 ( 0 hom. )

Consequence

MCFD2
ENST00000319466.9 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.300

Variant links:

Genes affected

MCFD2 (HGNC:18451): (multiple coagulation factor deficiency 2, ER cargo receptor complex subunit) This gene encodes a soluble luminal protein with two calmodulin-like EF-hand motifs at its C-terminus. This protein forms a complex with LMAN1 (lectin mannose binding protein 1; also known as ERGIC-53) that facilitates the transport of coagulation factors V (FV) and VIII (FVIII) from the endoplasmic reticulum to the Golgi apparatus via an endoplasmic reticulum Golgi intermediate compartment (ERGIC). Mutations in this gene cause combined deficiency of FV and FVIII (F5F8D); a rare autosomal recessive bleeding disorder characterized by mild to moderate bleeding and coordinate reduction in plasma FV and FVIII levels. This protein has also been shown to maintain stem cell potential in adult central nervous system and is a marker for testicular germ cell tumors. The 3' UTR of this gene contains a transposon-like human repeat element named 'THE 1'. A processed RNA pseudogene of this gene is on chromosome 6p22.1. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Apr 2016]

MCFD2 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 2-46902145-A-G is Benign according to our data. Variant chr2-46902145-A-G is described in ClinVar as [Benign]. Clinvar id is 336326.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MCFD2	NM_139279.6 linkuse as main transcript	c.*3318T>C		3_prime_UTR_variant	4/4	ENST00000319466.9	NP_644808.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MCFD2	ENST00000319466.9 linkuse as main transcript	c.*3318T>C		3_prime_UTR_variant	4/4	1	NM_139279.6	ENSP00000317271	P1	Q8NI22-1
	ENST00000429761.1 linkuse as main transcript	n.40+2831A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0586

AC:

8915

AN:

152176

Hom.:

447

Cov.:

show subpopulations

Gnomad AFR

AF:

0.124

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.0805

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.0930

Gnomad SAS

AF:

0.0513

Gnomad FIN

AF:

0.0421

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0186

Gnomad OTH

AF:

0.0431

GnomAD4 exome

AF:

0.0255

AC:

AN:

432

Hom.:

Cov.:

AF XY:

0.0346

AC XY:

AN XY:

260

show subpopulations

Gnomad4 FIN exome

AF:

0.0258

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0588

AC:

8954

AN:

152294

Hom.:

455

Cov.:

AF XY:

0.0609

AC XY:

4533

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.124

Gnomad4 AMR

AF:

0.0804

Gnomad4 ASJ

AF:

0.00259

Gnomad4 EAS

AF:

0.0934

Gnomad4 SAS

AF:

0.0516

Gnomad4 FIN

AF:

0.0421

Gnomad4 NFE

AF:

0.0186

Gnomad4 OTH

AF:

0.0422

Alfa

AF:

0.0294

Hom.:

182

Bravo

AF:

0.0648

Asia WGS

AF:

0.0840

AC:

292

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Factor 5 and Factor VIII, combined deficiency of, 2

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

-0.79

CADD

Benign

5.2

DANN

Benign

0.71

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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