rs10736303

Variant names:

• chr10-121574943-G-A
• rs10736303
• NM_000141.5:c.110-9239C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-121574943-G-A
• chr10-121574943-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000141.5(FGFR2):​c.110-9239C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 152,102 control chromosomes in the GnomAD database, including 14,657 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 0.41 (14657 hom., cov: 32)
• Consequence: FGFR2 NM_000141.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0810
• Publications: 31 publications found

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 Gene-Disease associations (from GenCC):

• Apert syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen, PanelApp Australia, G2P, Genomics England PanelApp
• Beare-Stevenson cutis gyrata syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen, G2P, Genomics England PanelApp
• Crouzon syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, ClinGen, PanelApp Australia, Genomics England PanelApp, G2P
• Jackson-Weiss syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, G2P
• LADD syndrome 1

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• Pfeiffer syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp, G2P
• Antley-Bixler syndrome without genital anomalies or disordered steroidogenesis

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp, G2P
• bent bone dysplasia syndrome 1

  Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet
• familial scaphocephaly syndrome, McGillivray type

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp
• Saethre-Chotzen syndrome

  Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia, Genomics England PanelApp
• Antley-Bixler syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• LADD syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Pfeiffer syndrome type 1

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Pfeiffer syndrome type 2

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Pfeiffer syndrome type 3

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.521 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGFR2	NM_000141.5	c.110-9239C>T		intron_variant	Intron 2 of 17	ENST00000358487.10	NP_000132.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGFR2	ENST00000358487.10	c.110-9239C>T		intron_variant	Intron 2 of 17	1	NM_000141.5	ENSP00000351276.6
FGFR2	ENST00000457416.7	c.110-9239C>T		intron_variant	Intron 2 of 17	1		ENSP00000410294.2
FGFR2	ENST00000369056.5	c.110-9239C>T		intron_variant	Intron 1 of 16	1		ENSP00000358052.1
FGFR2	ENST00000369058.7	c.110-9239C>T		intron_variant	Intron 2 of 16	1		ENSP00000358054.3
FGFR2	ENST00000613048.4	c.110-10364C>T		intron_variant	Intron 2 of 16	5		ENSP00000484154.1
FGFR2	ENST00000369061.8	c.110-9239C>T		intron_variant	Intron 1 of 14	1		ENSP00000358057.4
FGFR2	ENST00000369059.5	c.109+18766C>T		intron_variant	Intron 2 of 15	5		ENSP00000358055.1
FGFR2	ENST00000360144.7	c.110-10364C>T		intron_variant	Intron 2 of 16	2		ENSP00000353262.3
FGFR2	ENST00000604236.5	n.109+18766C>T		intron_variant	Intron 2 of 16	1		ENSP00000474109.1

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61667 AN: 151984 Hom.: 14643 Cov.: 32

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.371

Gnomad AMR AF: 0.483

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.448

Gnomad SAS AF: 0.478

Gnomad FIN AF: 0.496

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.525

Gnomad OTH AF: 0.418

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

GnomAD4 genome AF: 0.406 AC: 61694 AN: 152102 Hom.: 14657 Cov.: 32 AF XY: 0.406 AC XY: 30167 AN XY: 74342

African (AFR) AF: 0.139 AC: 5762 AN: 41518

American (AMR) AF: 0.483 AC: 7386 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.471 AC: 1633 AN: 3466

East Asian (EAS) AF: 0.449 AC: 2314 AN: 5156

South Asian (SAS) AF: 0.478 AC: 2307 AN: 4822

European-Finnish (FIN) AF: 0.496 AC: 5243 AN: 10564

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.525 AC: 35702 AN: 67974

Other (OTH) AF: 0.423 AC: 894 AN: 2112

Alfa AF: 0.480 Hom.: 10584

Bravo AF: 0.392

Asia WGS AF: 0.469 AC: 1630 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	9.0
DANN	Benign	0.83
PhyloP100		0.081
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10736303; hg19: chr10-123334457;