10-121538644-T-G

Position:

• chr10-121538644-T-G

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_000141.5(FGFR2):​c.696A>C​(p.Val232Val) 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. V232V) has been classified as Benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: FGFR2 NM_000141.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.206

Genes affected

FGFR2 (HGNC:3689): (fibroblast growth factor receptor 2) The protein encoded by this gene is a member of the fibroblast growth factor receptor family, where amino acid sequence is highly conserved between members and throughout evolution. FGFR family members differ from one another in their ligand affinities and tissue distribution. A full-length representative protein consists of an extracellular region, composed of three immunoglobulin-like domains, a single hydrophobic membrane-spanning segment and a cytoplasmic tyrosine kinase domain. The extracellular portion of the protein interacts with fibroblast growth factors, setting in motion a cascade of downstream signals, ultimately influencing mitogenesis and differentiation. This particular family member is a high-affinity receptor for acidic, basic and/or keratinocyte growth factor, depending on the isoform. Mutations in this gene are associated with Crouzon syndrome, Pfeiffer syndrome, Craniosynostosis, Apert syndrome, Jackson-Weiss syndrome, Beare-Stevenson cutis gyrata syndrome, Saethre-Chotzen syndrome, and syndromic craniosynostosis. Multiple alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Jan 2009]

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BP7: Synonymous conserved (PhyloP=0.206 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FGFR2	NM_000141.5	c.696A>C	p.Val232Val	synonymous_variant	6/18	ENST00000358487.10	NP_000132.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FGFR2	ENST00000358487.10	c.696A>C	p.Val232Val	synonymous_variant	6/18	1	NM_000141.5	ENSP00000351276.6
FGFR2	ENST00000457416.7	c.696A>C	p.Val232Val	synonymous_variant	6/18	1		ENSP00000410294.2
FGFR2	ENST00000369056.5	c.696A>C	p.Val232Val	synonymous_variant	5/17	1		ENSP00000358052.1
FGFR2	ENST00000369058.7	c.696A>C	p.Val232Val	synonymous_variant	6/17	1		ENSP00000358054.3
FGFR2	ENST00000613048.4	c.429A>C	p.Val143Val	synonymous_variant	5/17	5		ENSP00000484154.1
FGFR2	ENST00000369061.8	c.696A>C	p.Val232Val	synonymous_variant	5/15	1		ENSP00000358057.4
FGFR2	ENST00000369059.5	c.351A>C	p.Val117Val	synonymous_variant	4/16	5		ENSP00000358055.1
FGFR2	ENST00000360144.7	c.429A>C	p.Val143Val	synonymous_variant	5/17	2		ENSP00000353262.3
FGFR2	ENST00000604236.5	n.351A>C		non_coding_transcript_exon_variant	4/17	1		ENSP00000474109.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 55

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	9.8
DANN	Benign	0.77

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

LitVar

Other links and lift over

dbSNP: rs1047100; hg19: chr10-123298158;