chr5-128300920-G-T

Variant names:

• chr5-128300920-G-T
• rs149380208
• NM_001999.4:c.6063C>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001999.4(FBN2):​c.6063C>A​(p.Val2021Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. V2021V) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: FBN2 NM_001999.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24
• Publications: 0 publications found

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]

FBN2 Gene-Disease associations (from GenCC):

• congenital contractural arachnodactyly

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Orphanet, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp
• carpal tunnel syndrome

  Inheritance: AD Classification: LIMITED Submitted by: Franklin by Genoox
• familial thoracic aortic aneurysm and aortic dissection

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• macular degeneration, early-onset

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP7: Synonymous conserved (PhyloP=-1.24 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBN2	NM_001999.4	c.6063C>A	p.Val2021Val	synonymous_variant	Exon 48 of 65	ENST00000262464.9	NP_001990.2
FBN2	XM_017009228.3	c.5910C>A	p.Val1970Val	synonymous_variant	Exon 47 of 64		XP_016864717.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBN2	ENST00000262464.9	c.6063C>A	p.Val2021Val	synonymous_variant	Exon 48 of 65	1	NM_001999.4	ENSP00000262464.4
FBN2	ENST00000703783.1	n.2847C>A		non_coding_transcript_exon_variant	Exon 23 of 38
FBN2	ENST00000703785.1	n.2766C>A		non_coding_transcript_exon_variant	Exon 22 of 27

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	0.23
DANN	Benign	0.63
PhyloP100		-1.2

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs149380208; hg19: chr5-127636612;