2-162188192-AAC-GAT

Variant names:

• chr2-162188192-AAC-GAT
• NM_004460.5:c.1789_1791delGTTinsATC
• FAP p.Val597Ile

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_004460.5(FAP):​c.1789_1791delGTTinsATC​(p.Val597Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V597F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FAP NM_004460.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.90
• Publications: 0 publications found

Genes affected

FAP (HGNC:3590): (fibroblast activation protein alpha) The protein encoded by this gene is a homodimeric integral membrane gelatinase belonging to the serine protease family. It is selectively expressed in reactive stromal fibroblasts of epithelial cancers, granulation tissue of healing wounds, and malignant cells of bone and soft tissue sarcomas. This protein is thought to be involved in the control of fibroblast growth or epithelial-mesenchymal interactions during development, tissue repair, and epithelial carcinogenesis. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2014]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004460.5. 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
	FAP	NM_004460.5	MANE Select	c.1789_1791delGTTinsATC	p.Val597Ile	missense	N/A	NP_004451.2
	FAP	NM_001291807.3		c.1714_1716delGTTinsATC	p.Val572Ile	missense	N/A	NP_001278736.1	B4DLR2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAP	ENST00000188790.9	TSL:1 MANE Select	c.1789_1791delGTTinsATC	p.Val597Ile	missense	N/A	ENSP00000188790.4	Q12884-1
	FAP	ENST00000422436.5	TSL:1	n.*670_*672delGTTinsATC		non_coding_transcript_exon	Exon 7 of 13	ENSP00000417028.1	H7C4D9
	FAP	ENST00000422436.5	TSL:1	n.*670_*672delGTTinsATC		3_prime_UTR	Exon 7 of 13	ENSP00000417028.1	H7C4D9

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.9

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr2-163044702;