rs587777726
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PVS1_ModeratePM2PP3_StrongPP5
The ENST00000335110.5(FAT4):c.2094-2A>C variant causes a splice acceptor change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Consequence
FAT4
ENST00000335110.5 splice_acceptor
ENST00000335110.5 splice_acceptor
Scores
3
1
3
Splicing: ADA: 0.9997
1
Clinical Significance
Conservation
PhyloP100: 5.65
Genes affected
FAT4 (HGNC:23109): (FAT atypical cadherin 4) The protein encoded by this gene is a member of the protocadherin family. This gene may play a role in regulating planar cell polarity (PCP). Studies in mice suggest that loss of PCP signaling may cause cystic kidney disease, and mutations in this gene have been associated with Van Maldergem Syndrome 2. Alternatively spliced transcript variants have been noted for this gene. [provided by RefSeq, Mar 2014]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
PVS1
?
Splicing variant, NOT destroyed by nmd, known LOF gene, truncates exone, which is 0.025235288 fraction of the gene. Cryptic splice site detected, with MaxEntScore 9, offset of -6, new splice context is: atttctgctttctgctttAGtta. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
BayesDel_addAF computational evidence supports a deleterious effect, 0.625
PP5
?
Variant 4-125446297-A-C is Pathogenic according to our data. Variant chr4-125446297-A-C is described in ClinVar as [Pathogenic]. Clinvar id is 156112.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FAT4 | NM_001291303.3 | c.7204A>C | p.Arg2402= | synonymous_variant | 9/18 | ENST00000394329.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FAT4 | ENST00000335110.5 | c.2094-2A>C | splice_acceptor_variant | 1 | |||||
FAT4 | ENST00000394329.9 | c.7204A>C | p.Arg2402= | synonymous_variant | 9/18 | 5 | NM_001291303.3 | P1 | |
FAT4 | ENST00000674496.2 | c.1975A>C | p.Arg659= | synonymous_variant | 8/17 | ||||
FAT4 | ENST00000509444.1 | n.187A>C | non_coding_transcript_exon_variant | 1/2 | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Hennekam lymphangiectasia-lymphedema syndrome 2 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 01, 2014 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
MutationTaster
Benign
D;D
GERP RS
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AL_spliceai
Position offset: 2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at