rs2468844

Variant names:

• chr11-18245480-C-A
• rs2468844
• NM_030754.5:c.266G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-18245480-C-A
• chr11-18245480-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_030754.5(SAA2):​c.266G>T​(p.Arg89Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SAA2 NM_030754.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.93
• Publications: 36 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11527264).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030754.5. 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
	SAA2	NM_030754.5	MANE Select	c.266G>T	p.Arg89Leu	missense	Exon 4 of 4	NP_110381.2	P0DJI9-1
	SAA2	NM_001385666.1		c.266G>T	p.Arg89Leu	missense	Exon 5 of 5	NP_001372595.1	P0DJI9-1
	SAA2	NM_001385668.1		c.127G>T	p.Val43Leu	missense	Exon 3 of 3	NP_001372597.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAA2	ENST00000256733.9	TSL:1 MANE Select	c.266G>T	p.Arg89Leu	missense	Exon 4 of 4	ENSP00000256733.5	P0DJI9-1
	SAA2-SAA4	ENST00000524555.3	TSL:3	c.230+430G>T		intron	N/A	ENSP00000485552.1	A0A096LPE2
	SAA2	ENST00000414546.6	TSL:1	c.230+430G>T		intron	N/A	ENSP00000416716.2	P0DJI9-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 60

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.54
DANN	Benign	0.85
DEOGEN2	Benign	0.31	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.048	N
LIST_S2	Benign	0.073	T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	2.0	M
PhyloP100		-3.9
PROVEAN	Uncertain	-4.2	D
REVEL	Benign	0.063
Sift	Benign	0.14	T
Sift4G	Benign	0.18	T
Vest4		0.085
MutPred		0.65		Loss of MoRF binding (P = 0.0071)
MVP		0.014
MPC		0.025
ClinPred		0.23	T
GERP RS		-10
Varity_R		0.14
gMVP		0.38
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2468844; hg19: chr11-18267027;