chr4-15962514-A-T

Position:

• chr4-15962514-A-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_031950.4(FGFBP2):​c.616T>A​(p.Cys206Ser) variant causes a missense 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 Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: FGFBP2 NM_031950.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.83

Genes affected

FGFBP2 (HGNC:29451): (fibroblast growth factor binding protein 2) This gene encodes a member of the fibroblast growth factor binding protein family. The encoded protein is a serum protein that is selectively secreted by cytotoxic lymphocytes and may be involved in cytotoxic lymphocyte-mediated immunity. An increase in the amount of gene product may be associated with atopic asthma and mild extrinsic asthma.[provided by RefSeq Staff, Oct 2008]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.942

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FGFBP2	NM_031950.4	c.616T>A	p.Cys206Ser	missense_variant	1/2	ENST00000259989.7	NP_114156.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FGFBP2	ENST00000259989.7	c.616T>A	p.Cys206Ser	missense_variant	1/2	1	NM_031950.4	ENSP00000259989	P1
FGFBP2	ENST00000509331.1	n.83-1903T>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 07, 2022

The c.616T>A (p.C206S) alteration is located in exon 1 (coding exon 1) of the FGFBP2 gene. This alteration results from a T to A substitution at nucleotide position 616, causing the cysteine (C) at amino acid position 206 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.84
BayesDel_addAF	Benign	-0.063	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	20
DANN	Benign	0.81
DEOGEN2	Benign	0.18	T
Eigen	Benign	0.0028
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.28	T
M_CAP	Benign	0.0092	T
MetaRNN	Pathogenic	0.94	D
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	1.0	L
MutationTaster	Benign	1.0	D
PrimateAI	Benign	0.36	T
PROVEAN	Pathogenic	-9.1	D
REVEL	Uncertain	0.30
Sift	Uncertain	0.0090	D
Sift4G	Benign	0.21	T
Polyphen		1.0	D
Vest4		0.47
MutPred		0.86		Loss of catalytic residue at W207 (P = 0.0055);
MVP		0.60
MPC		0.76
ClinPred		0.98	D
GERP RS		2.7
Varity_R		0.33
gMVP		0.91

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-15964137;