rs3135749

Positions:

• chr10-121550306-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000141.5(FGFR2):​c.624+984T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0867 in 152,184 control chromosomes in the GnomAD database, including 1,508 homozygotes. 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: 𝑓 0.087 (1508 hom., cov: 32)
• Consequence: FGFR2 NM_000141.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.513

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]

FGFR2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FGFR2	NM_000141.5	c.624+984T>C		intron_variant		ENST00000358487.10	NP_000132.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FGFR2	ENST00000358487.10	c.624+984T>C		intron_variant		1	NM_000141.5	ENSP00000351276.6
FGFR2	ENST00000457416.7	c.624+984T>C		intron_variant		1		ENSP00000410294.2
FGFR2	ENST00000369056.5	c.624+984T>C		intron_variant		1		ENSP00000358052.1
FGFR2	ENST00000369058.7	c.624+984T>C		intron_variant		1		ENSP00000358054.3
FGFR2	ENST00000613048.4	c.357+984T>C		intron_variant		5		ENSP00000484154.1
FGFR2	ENST00000369061.8	c.624+984T>C		intron_variant		1		ENSP00000358057.4
FGFR2	ENST00000369059.5	c.279+984T>C		intron_variant		5		ENSP00000358055.1
FGFR2	ENST00000360144.7	c.357+984T>C		intron_variant		2		ENSP00000353262.3
FGFR2	ENST00000604236.5	n.279+984T>C		intron_variant		1		ENSP00000474109.1

Frequencies

GnomAD3 genomes AF: 0.0864 AC: 13138 AN: 152066 Hom.: 1495 Cov.: 32

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.0396

Gnomad AMR AF: 0.0766

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.0732

Gnomad SAS AF: 0.00725

Gnomad FIN AF: 0.0302

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00226

Gnomad OTH AF: 0.0647

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0867 AC: 13195 AN: 152184 Hom.: 1508 Cov.: 32 AF XY: 0.0863 AC XY: 6422 AN XY: 74404

Gnomad4 AFR AF: 0.264

Gnomad4 AMR AF: 0.0775

Gnomad4 ASJ AF: 0.00461

Gnomad4 EAS AF: 0.0724

Gnomad4 SAS AF: 0.00746

Gnomad4 FIN AF: 0.0302

Gnomad4 NFE AF: 0.00226

Gnomad4 OTH AF: 0.0645

Alfa AF: 0.0350 Hom.: 123

Bravo AF: 0.0999

Asia WGS AF: 0.0520 AC: 182 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	4.6
DANN	Benign	0.45

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: rs3135749; hg19: chr10-123309820;