rs2912753

Variant names:

• chr10-121497888-A-C
• rs2912753
• NM_022970.4:c.1675+607T>G

Your query was ambiguous. Multiple possible variants found:

• chr10-121497888-A-C
• chr10-121497888-A-G
• chr10-121497888-A-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.1672+607T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.894 in 152,252 control chromosomes in the GnomAD database, including 61,356 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 0.89 (61356 hom., cov: 33)
• Consequence: FGFR2 NM_000141.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36
• Publications: 6 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: ClinGen, Genomics England PanelApp, G2P, Orphanet
• Beare-Stevenson cutis gyrata syndrome

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

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen
• Crouzon syndrome

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

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

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

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

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp, G2P
• familial scaphocephaly syndrome, McGillivray type

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

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

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

  Inheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, ClinGen
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.973 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000141.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGFR2	NM_022970.4	MANE Plus Clinical	c.1675+607T>G		intron	N/A	NP_075259.4	P21802-3
	FGFR2	NM_000141.5	MANE Select	c.1672+607T>G		intron	N/A	NP_000132.3	P21802-1
	FGFR2	NM_001441087.1		c.1669+607T>G		intron	N/A	NP_001428016.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGFR2	ENST00000457416.7	TSL:1 MANE Plus Clinical	c.1675+607T>G		intron	N/A	ENSP00000410294.2	P21802-3
	FGFR2	ENST00000358487.10	TSL:1 MANE Select	c.1672+607T>G		intron	N/A	ENSP00000351276.6	P21802-1
	FGFR2	ENST00000369056.5	TSL:1	c.1675+607T>G		intron	N/A	ENSP00000358052.1	P21802-17

Frequencies

GnomAD3 genomes AF: 0.894 AC: 135954 AN: 152134 Hom.: 61315 Cov.: 33

Gnomad AFR AF: 0.754

Gnomad AMI AF: 0.911

Gnomad AMR AF: 0.944

Gnomad ASJ AF: 0.934

Gnomad EAS AF: 0.996

Gnomad SAS AF: 0.960

Gnomad FIN AF: 0.937

Gnomad MID AF: 0.930

Gnomad NFE AF: 0.944

Gnomad OTH AF: 0.924

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

GnomAD4 genome AF: 0.894 AC: 136048 AN: 152252 Hom.: 61356 Cov.: 33 AF XY: 0.896 AC XY: 66667 AN XY: 74436

African (AFR) AF: 0.754 AC: 31322 AN: 41522

American (AMR) AF: 0.944 AC: 14431 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.934 AC: 3242 AN: 3472

East Asian (EAS) AF: 0.996 AC: 5162 AN: 5182

South Asian (SAS) AF: 0.961 AC: 4635 AN: 4824

European-Finnish (FIN) AF: 0.937 AC: 9954 AN: 10620

Middle Eastern (MID) AF: 0.932 AC: 274 AN: 294

European-Non Finnish (NFE) AF: 0.944 AC: 64241 AN: 68024

Other (OTH) AF: 0.924 AC: 1956 AN: 2116

Alfa AF: 0.932 Hom.: 105049

Bravo AF: 0.888

Asia WGS AF: 0.968 AC: 3368 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.66
DANN	Benign	0.41
PhyloP100		-1.4
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: rs2912753; hg19: chr10-123257402;