rs370851605
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Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2
The NM_001999.4(FBN2):c.8112C>T(p.Asn2704=) variant causes a synonymous change. The variant allele was found at a frequency of 0.0000359 in 1,614,130 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000032 ( 1 hom. )
Consequence
FBN2
NM_001999.4 synonymous
NM_001999.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 3.62
Genes affected
FBN2 (HGNC:3604): (fibrillin 2) The protein encoded by this gene is a component of connective tissue microfibrils and may be involved in elastic fiber assembly. Mutations in this gene cause congenital contractural arachnodactyly. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -18 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.36).
BP6
?
Variant 5-128263505-G-A is Benign according to our data. Variant chr5-128263505-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 258528.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0000722 (11/152258) while in subpopulation AMR AF= 0.000654 (10/15296). AF 95% confidence interval is 0.000354. There are 0 homozygotes in gnomad4. There are 8 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 11 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FBN2 | NM_001999.4 | c.8112C>T | p.Asn2704= | synonymous_variant | 63/65 | ENST00000262464.9 | |
FBN2 | XM_017009228.3 | c.7959C>T | p.Asn2653= | synonymous_variant | 62/64 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FBN2 | ENST00000262464.9 | c.8112C>T | p.Asn2704= | synonymous_variant | 63/65 | 1 | NM_001999.4 | P1 | |
FBN2 | ENST00000703782.1 | n.227C>T | non_coding_transcript_exon_variant | 2/2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000723 AC: 11AN: 152140Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000358 AC: 9AN: 251272Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135796
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GnomAD4 exome AF: 0.0000322 AC: 47AN: 1461872Hom.: 1 Cov.: 31 AF XY: 0.0000248 AC XY: 18AN XY: 727240
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GnomAD4 genome ? AF: 0.0000722 AC: 11AN: 152258Hom.: 0 Cov.: 32 AF XY: 0.000107 AC XY: 8AN XY: 74434
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Familial thoracic aortic aneurysm and aortic dissection Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 09, 2022 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Congenital contractural arachnodactyly Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 08, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at