11-18245479-ACG-TAA

Variant names:

• chr11-18245479-ACG-TAA
• NM_030754.5:c.265_267delCGTinsTTA
• SAA2 p.Arg89Leu

Variant summary

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

The NM_001385668.1(SAA2):​c.126_128delCGTinsTTA​(p.Val43*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. 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. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SAA2 NM_001385668.1 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.618
• Publications: 0 publications found

Genes affected

SAA2 (HGNC:10514): (serum amyloid A2) This gene encodes a member of the serum amyloid A family of apolipoproteins. The encoded preproprotein is proteolytically processed to generate the mature protein. This protein is a major acute phase protein that is highly expressed in response to inflammation and tissue injury. This protein also plays an important role in HDL metabolism and cholesterol homeostasis. High levels of this protein are associated with chronic inflammatory diseases including atherosclerosis, rheumatoid arthritis, Alzheimer's disease and Crohn's disease. This protein may also be a potential biomarker for certain tumors. Finally, antimicrobial activity against S. aureus and E. coli resides in the N-terminal portion of the mature protein. [provided by RefSeq, Jul 2020]

SAA2-SAA4 (HGNC:39550): (SAA2-SAA4 readthrough) This locus represents naturally occurring read-through transcription between the neighboring serum amyloid A2 and serum amyloid A4 genes on chromosome 11. The read-through transcript produces a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Dec 2010]

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001385668.1. 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
	SAA2	NM_030754.5	MANE Select	c.265_267delCGTinsTTA	p.Arg89Leu	missense	N/A	NP_110381.2	P0DJI9-1
	SAA2	NM_001385668.1		c.126_128delCGTinsTTA	p.Val43*	stop_gained	N/A	NP_001372597.1
	SAA2	NM_001385673.1		c.33_35delCGTinsTTA	p.Val12*	stop_gained	N/A	NP_001372602.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAA2	ENST00000256733.9	TSL:1 MANE Select	c.265_267delCGTinsTTA	p.Arg89Leu	missense	N/A	ENSP00000256733.5	P0DJI9-1
	SAA2-SAA4	ENST00000524555.3	TSL:3	c.230+429_230+431delCGTinsTTA		intron	N/A	ENSP00000485552.1	A0A096LPE2
	SAA2	ENST00000414546.6	TSL:1	c.230+429_230+431delCGTinsTTA		intron	N/A	ENSP00000416716.2	P0DJI9-2

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.62

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: chr11-18267026;