10-121520281-C-G

Variant names:

• chr10-121520281-C-G
• NM_000141.5:c.749-112G>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000141.5(FGFR2):​c.749-112G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000102 in 982,046 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000010 (0 hom.)
• Consequence: FGFR2 NM_000141.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.324

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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGFR2	NM_000141.5	c.749-112G>C		intron_variant	Intron 6 of 17	ENST00000358487.10	NP_000132.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGFR2	ENST00000358487.10	c.749-112G>C		intron_variant	Intron 6 of 17	1	NM_000141.5	ENSP00000351276.6
FGFR2	ENST00000457416.7	c.749-112G>C		intron_variant	Intron 6 of 17	1		ENSP00000410294.2
FGFR2	ENST00000369056.5	c.749-112G>C		intron_variant	Intron 5 of 16	1		ENSP00000358052.1
FGFR2	ENST00000369058.7	c.749-112G>C		intron_variant	Intron 6 of 16	1		ENSP00000358054.3
FGFR2	ENST00000613048.4	c.482-112G>C		intron_variant	Intron 5 of 16	5		ENSP00000484154.1
FGFR2	ENST00000369061.8	c.749-4962G>C		intron_variant	Intron 5 of 14	1		ENSP00000358057.4
FGFR2	ENST00000369059.5	c.404-112G>C		intron_variant	Intron 4 of 15	5		ENSP00000358055.1
FGFR2	ENST00000360144.7	c.482-112G>C		intron_variant	Intron 5 of 16	2		ENSP00000353262.3
FGFR2	ENST00000478859.5	c.65-112G>C		intron_variant	Intron 5 of 16	1		ENSP00000474011.1
FGFR2	ENST00000604236.5	n.404-112G>C		intron_variant	Intron 4 of 16	1		ENSP00000474109.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000102 AC: 1 AN: 982046 Hom.: 0 AF XY: 0.00000206 AC XY: 1 AN XY: 486530

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000177

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	11
DANN	Benign	0.44

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: chr10-123279795;