chrX-155026934-TGGGAATGGAAACATCTGCCCCACGTGCCGGAAGCCAAGTGGTGGCGACAACTGCGCGCCACTCCGCGGCCTACCGCGCAGATCCTCTACGTGTGTCCTCGCGAGACAAGCTCACCGAAATGGCCGCGTCCAGTCAAGGTAAGGGCGGGCGCGCGCGCGGCCGGCGCCGCGGGGAGCCGCCTTCCTG-T
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_StrongPM2PP5
The NM_023934.4(FUNDC2):c.-2_133+51del variant causes a splice donor, splice donor 5th base, coding sequence, 5 prime UTR, intron change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 23)
Consequence
FUNDC2
NM_023934.4 splice_donor, splice_donor_5th_base, coding_sequence, 5_prime_UTR, intron
NM_023934.4 splice_donor, splice_donor_5th_base, coding_sequence, 5_prime_UTR, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.36
Genes affected
FUNDC2 (HGNC:24925): (FUN14 domain containing 2) Predicted to be involved in autophagy of mitochondrion. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]
F8 (HGNC:3546): (coagulation factor VIII) This gene encodes coagulation factor VIII, which participates in the intrinsic pathway of blood coagulation; factor VIII is a cofactor for factor IXa which, in the presence of Ca+2 and phospholipids, converts factor X to the activated form Xa. This gene produces two alternatively spliced transcripts. Transcript variant 1 encodes a large glycoprotein, isoform a, which circulates in plasma and associates with von Willebrand factor in a noncovalent complex. This protein undergoes multiple cleavage events. Transcript variant 2 encodes a putative small protein, isoform b, which consists primarily of the phospholipid binding domain of factor VIIIc. This binding domain is essential for coagulant activity. Defects in this gene results in hemophilia A, a common recessive X-linked coagulation disorder. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
PVS1
Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.3982456 fraction of the gene.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant X-155026934-TGGGAATGGAAACATCTGCCCCACGTGCCGGAAGCCAAGTGGTGGCGACAACTGCGCGCCACTCCGCGGCCTACCGCGCAGATCCTCTACGTGTGTCCTCGCGAGACAAGCTCACCGAAATGGCCGCGTCCAGTCAAGGTAAGGGCGGGCGCGCGCGCGGCCGGCGCCGCGGGGAGCCGCCTTCCTG-T is Pathogenic according to our data. Variant chrX-155026934-TGGGAATGGAAACATCTGCCCCACGTGCCGGAAGCCAAGTGGTGGCGACAACTGCGCGCCACTCCGCGGCCTACCGCGCAGATCCTCTACGTGTGTCCTCGCGAGACAAGCTCACCGAAATGGCCGCGTCCAGTCAAGGTAAGGGCGGGCGCGCGCGCGGCCGGCGCCGCGGGGAGCCGCCTTCCTG-T is described in ClinVar as [Pathogenic]. Clinvar id is 973793.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FUNDC2 | NM_023934.4 | c.-2_133+51del | splice_donor_variant, splice_donor_5th_base_variant, coding_sequence_variant, 5_prime_UTR_variant, intron_variant | 1/5 | ENST00000369498.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FUNDC2 | ENST00000369498.8 | c.-2_133+51del | splice_donor_variant, splice_donor_5th_base_variant, coding_sequence_variant, 5_prime_UTR_variant, intron_variant | 1/5 | 1 | NM_023934.4 | P1 | ||
F8 | ENST00000423959.5 | 5_prime_UTR_variant | 1/6 | 3 | |||||
FUNDC2 | ENST00000475165.5 | n.242+257_242+442del | intron_variant, non_coding_transcript_variant | 3 | |||||
FUNDC2 | ENST00000484175.5 | upstream_gene_variant | 3 |
Frequencies
GnomAD3 genomes Cov.: 23
GnomAD3 genomes
Cov.:
23
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome Cov.: 23
GnomAD4 genome
Cov.:
23
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Hereditary factor VIII deficiency disease Pathogenic:1
Pathogenic, no assertion criteria provided | clinical testing | Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico | Jun 01, 2019 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at