rs2912753

Variant names:

• chr10-121497888-A-C
• rs2912753
• NM_000141.5:c.1672+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. Variant got -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

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 Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGFR2	NM_000141.5	c.1672+607T>G		intron_variant	Intron 12 of 17	ENST00000358487.10	NP_000132.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGFR2	ENST00000358487.10	c.1672+607T>G		intron_variant	Intron 12 of 17	1	NM_000141.5	ENSP00000351276.6
FGFR2	ENST00000457416.7	c.1675+607T>G		intron_variant	Intron 12 of 17	1		ENSP00000410294.2
FGFR2	ENST00000369056.5	c.1675+607T>G		intron_variant	Intron 11 of 16	1		ENSP00000358052.1
FGFR2	ENST00000369058.7	c.1675+607T>G		intron_variant	Intron 12 of 16	1		ENSP00000358054.3
FGFR2	ENST00000613048.4	c.1405+607T>G		intron_variant	Intron 11 of 16	5		ENSP00000484154.1
FGFR2	ENST00000369061.8	c.1336+607T>G		intron_variant	Intron 9 of 14	1		ENSP00000358057.4
FGFR2	ENST00000369059.5	c.1330+607T>G		intron_variant	Intron 10 of 15	5		ENSP00000358055.1
FGFR2	ENST00000360144.7	c.1408+607T>G		intron_variant	Intron 11 of 16	2		ENSP00000353262.3
FGFR2	ENST00000478859.5	c.988+607T>G		intron_variant	Intron 11 of 16	1		ENSP00000474011.1
FGFR2	ENST00000429361.5	c.448+607T>G		intron_variant	Intron 4 of 8	5		ENSP00000404219.1
FGFR2	ENST00000604236.5	n.*719+607T>G		intron_variant	Intron 11 of 16	1		ENSP00000474109.1

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

Gnomad4 AFR AF: 0.754

Gnomad4 AMR AF: 0.944

Gnomad4 ASJ AF: 0.934

Gnomad4 EAS AF: 0.996

Gnomad4 SAS AF: 0.961

Gnomad4 FIN AF: 0.937

Gnomad4 NFE AF: 0.944

Gnomad4 OTH AF: 0.924

Alfa AF: 0.936 Hom.: 73283

Bravo AF: 0.888

Asia WGS AF: 0.968 AC: 3368 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.66
DANN	Benign	0.41

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: rs2912753; hg19: chr10-123257402;