rs3135774

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000141.5(FGFR2):c.1288-23G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00843 in 1,613,614 control chromosomes in the GnomAD database, including 373 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 82 hom., cov: 32)

Exomes 𝑓: 0.0077 ( 291 hom. )

Consequence

FGFR2
NM_000141.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.722

Variant links:

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 links:

FGFR2 (HGNC:):

FGFR2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 10-121503964-C-G is Benign according to our data. Variant chr10-121503964-C-G is described in ClinVar as [Benign]. Clinvar id is 675995.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-121503964-C-G is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0753 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FGFR2	NM_000141.5 linkuse as main transcript	c.1288-23G>C		intron_variant		ENST00000358487.10	NP_000132.3	P21802-1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
FGFR2	ENST00000358487.10 linkuse as main transcript	c.1288-23G>C	intron_variant	1	NM_000141.5	ENSP00000351276.6	P21802-1
FGFR2	ENST00000457416.7 linkuse as main transcript	c.1291-23G>C	intron_variant	1		ENSP00000410294.2	P21802-3
FGFR2	ENST00000369056.5 linkuse as main transcript	c.1291-23G>C	intron_variant	1		ENSP00000358052.1	P21802-17
FGFR2	ENST00000369058.7 linkuse as main transcript	c.1291-23G>C	intron_variant	1		ENSP00000358054.3	A0A5S6RJB7
FGFR2	ENST00000613048.4 linkuse as main transcript	c.1021-23G>C	intron_variant	5		ENSP00000484154.1	D2CGD1
FGFR2	ENST00000369061.8 linkuse as main transcript	c.952-23G>C	intron_variant	1		ENSP00000358057.4	P21802-23
FGFR2	ENST00000369059.5 linkuse as main transcript	c.946-23G>C	intron_variant	5		ENSP00000358055.1	E7EVR7
FGFR2	ENST00000360144.7 linkuse as main transcript	c.1024-23G>C	intron_variant	2		ENSP00000353262.3	P21802-22
FGFR2	ENST00000478859.5 linkuse as main transcript	c.604-23G>C	intron_variant	1		ENSP00000474011.1	S4R381
FGFR2	ENST00000429361.5 linkuse as main transcript	c.64-23G>C	intron_variant	5		ENSP00000404219.1	H7C265
FGFR2	ENST00000604236.5 linkuse as main transcript	n.*335-23G>C	intron_variant	1		ENSP00000474109.1	S4R3B2

Frequencies

GnomAD3 genomes

AF:

0.0158

AC:

2397

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0178

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0783

Gnomad ASJ

AF:

0.0156

Gnomad EAS

AF:

0.0160

Gnomad SAS

AF:

0.0139

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00313

Gnomad OTH

AF:

0.0206

GnomAD3 exomes

AF:

0.0207

AC:

5162

AN:

249812

Hom.:

216

AF XY:

0.0173

AC XY:

2333

AN XY:

135074

show subpopulations

Gnomad AFR exome

AF:

0.0181

Gnomad AMR exome

AF:

0.103

Gnomad ASJ exome

AF:

0.0165

Gnomad EAS exome

AF:

0.0194

Gnomad SAS exome

AF:

0.00948

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00352

Gnomad OTH exome

AF:

0.0203

GnomAD4 exome

AF:

0.00765

AC:

11180

AN:

1461384

Hom.:

291

Cov.:

AF XY:

0.00743

AC XY:

5398

AN XY:

726970

show subpopulations

Gnomad4 AFR exome

AF:

0.0206

Gnomad4 AMR exome

AF:

0.0992

Gnomad4 ASJ exome

AF:

0.0168

Gnomad4 EAS exome

AF:

0.0183

Gnomad4 SAS exome

AF:

0.0101

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.00290

Gnomad4 OTH exome

AF:

0.0109

GnomAD4 genome

AF:

0.0159

AC:

2418

AN:

152230

Hom.:

Cov.:

AF XY:

0.0173

AC XY:

1289

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.0179

Gnomad4 AMR

AF:

0.0790

Gnomad4 ASJ

AF:

0.0156

Gnomad4 EAS

AF:

0.0159

Gnomad4 SAS

AF:

0.0143

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00313

Gnomad4 OTH

AF:

0.0203

Alfa

AF:

0.00543

Hom.:

Bravo

AF:

0.0221

Asia WGS

AF:

0.0160

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

DANN

Benign

0.58

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over