3-12609348-TA-TAAA
Variant summary
Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2
The NM_002880.4(RAF1):c.321-15_321-14dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
RAF1
NM_002880.4 intron
NM_002880.4 intron
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.987
Publications
0 publications found
Genes affected
RAF1 (HGNC:9829): (Raf-1 proto-oncogene, serine/threonine kinase) This gene is the cellular homolog of viral raf gene (v-raf). The encoded protein is a MAP kinase kinase kinase (MAP3K), which functions downstream of the Ras family of membrane associated GTPases to which it binds directly. Once activated, the cellular RAF1 protein can phosphorylate to activate the dual specificity protein kinases MEK1 and MEK2, which in turn phosphorylate to activate the serine/threonine specific protein kinases, ERK1 and ERK2. Activated ERKs are pleiotropic effectors of cell physiology and play an important role in the control of gene expression involved in the cell division cycle, apoptosis, cell differentiation and cell migration. Mutations in this gene are associated with Noonan syndrome 5 and LEOPARD syndrome 2. [provided by RefSeq, Jul 2008]
RAF1 Gene-Disease associations (from GenCC):
- Noonan syndromeInheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
- Noonan syndrome 5Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia, G2P
- dilated cardiomyopathy 1NNInheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
- LEOPARD syndrome 2Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
- familial isolated dilated cardiomyopathyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- Noonan syndrome with multiple lentiginesInheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, ClinGen
- cardiofaciocutaneous syndromeInheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
- Costello syndromeInheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
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ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1399138Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0AN XY: 699500
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1399138
Hom.:
Cov.:
25
AF XY:
AC XY:
0
AN XY:
699500
African (AFR)
AF:
AC:
0
AN:
32172
American (AMR)
AF:
AC:
0
AN:
44586
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25800
East Asian (EAS)
AF:
AC:
0
AN:
39340
South Asian (SAS)
AF:
AC:
0
AN:
84896
European-Finnish (FIN)
AF:
AC:
0
AN:
53268
Middle Eastern (MID)
AF:
AC:
0
AN:
5662
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1055058
Other (OTH)
AF:
AC:
0
AN:
58356
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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