rs2070600

Variant names:

• chr6-32183666-C-T
• rs2070600
• NM_001136.5:c.244G>A
• AGER p.Gly82Ser

Your query was ambiguous. Multiple possible variants found:

• chr6-32183666-C-T
• chr6-32183666-C-A
• chr6-32183666-C-G

GermlineCancer (beta)

Variant summary

Our verdict is Benign.

-7 Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received -7 classification points (ACMG Germline Pathogenicity v2019). BA1PP3

The NM_001136.5(AGER):c.244G>A (p.Gly82Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.0561 (AC=90,557) in the gnomAD database across 1,613,010 control chromosomes, including 3,365 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.196. In-silico predictor (REVEL) classifies this variant as likely benign. Variant has been reported in ClinVar as Uncertain Significance (no review stars). This exact variant is curated in the UniProt human variants database as Uncertain Significance; it is also listed as a COSMIC curated somatic variant.

• Frequency:
  • Genomes: 𝑓 0.039 (234 hom., cov: 33)
  • Exomes 𝑓: 0.058 (3131 hom.)
• Consequence: AGER NM_001136.5 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 2.46
• Publications: 472 publications found

Genes affected

AGER (HGNC:320): (advanced glycosylation end-product specific receptor) The advanced glycosylation end product (AGE) receptor encoded by this gene is a member of the immunoglobulin superfamily of cell surface receptors. It is a multiligand receptor, and besides AGE, interacts with other molecules implicated in homeostasis, development, and inflammation, and certain diseases, such as diabetes and Alzheimer's disease. Many alternatively spliced transcript variants encoding different isoforms, as well as non-protein-coding variants, have been described for this gene (PMID:18089847). [provided by RefSeq, May 2011]

Classification according to ACMG Germline Pathogenicity v2019

Our verdict: Benign. The variant received -7 points.

• PP3: Splicing predictors (SpliceAI/dbscSNV) support splicing impact — supporting computational evidence (PP3); Splicing verdict: pathogenic (Supporting).; Germline computational verdict: not pathogenic.
• BA1: GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.1958 — exceeds 5%% threshold (BA1 applied)

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_001136.5. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGER	NM_001136.5	MANE Select	c.244G>A	p.Gly82Ser	missense	Exon 3 of 11	NP_001127.1	Q15109-1
	AGER	NM_001206929.2		c.244G>A	p.Gly82Ser	missense	Exon 3 of 11	NP_001193858.1	Q15109-6
	AGER	NM_001206932.2		c.202G>A	p.Gly68Ser	missense	Exon 3 of 11	NP_001193861.1	Q15109-7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGER	ENST00000375076.9	TSL:1 MANE Select	c.244G>A	p.Gly82Ser	missense	Exon 3 of 11	ENSP00000364217.4	Q15109-1
	AGER	ENST00000375069.7	TSL:1	c.244G>A	p.Gly82Ser	missense	Exon 3 of 11	ENSP00000364210.4	Q15109-6
	AGER	ENST00000438221.6	TSL:1	c.244G>A	p.Gly82Ser	missense	Exon 3 of 10	ENSP00000387887.2	Q15109-4

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 6 sources Large-scale international reference populations
GnomAD3 genomes	0.0388	5905	234	152132	33
GnomAD2 exomes	0.0532	13091		245924
GnomAD4 exome	0.0580	84662	3131	1460760	36
GnomAD4 genome	0.0387	5895	234	152250	33
TOPMed (Bravo)	0.0339
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	0.0429	22085	767	515214
Local & regional cohorts 9 sources Population-specific and national genomic databases
ABraOM SABE-WGS-1171	0.0179	42	1	2342
ESP6500 (Exome Variant Server)	0.0349	294		8430
GenomeAsia100K	0.104	361		3478
Korea4K (4,157 Koreans)	0.159	1149		7234
Qatari Genome	0.0204	41		2010
ToMMo 61KJPN (+60KJPN MNV)	0.153	18670	1442	122192
Turkish Variome	0.0395	61	2	1546
UK10K	0.0731	553		7562
WBBC (Westlake BioBank for Chinese) pilot	0.254	2272	268	8960

Showing 15 sources

Case/control cohorts

Cohort	Cases			Controls
	AF	AC	AN	AF	AC	AN
ASC(Autism)	0.0514 *	494	9620	0.0484 *	505	10424
BipEx(Bipolar disorder (including schizoaffective))	0.0550	1562	28420	0.0564	1627	28844
Epi25(Epilepsy)	0.0534	2242	41958	0.0496	3317	66888
SCHEMA(Schizophrenia)	0.0837	10740	128388	0.0666	13132	197070

Showing 4 cohortsAllele count / allele number. AF is computed from the counts for ASC (not provided by the source).

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	COPD, severe early onset (1)

Computational Scores

Algorithm	Calibrated prediction	Prediction	Score
AlphaGenome AVI	Pathogenic	-	32
AlphaMissense	Benign	-	0.31
BayesDel_addAF	Benign	T	-0.52
BayesDel_noAF	Benign	-	-0.37
CADD	Pathogenic	-	34
DANN	Uncertain	-	1.0
DEOGEN2	Benign	T	0.11
Eigen	Uncertain	-	0.67
Eigen_PC	Pathogenic	-	0.68
FATHMM_MKL	Uncertain	D	0.88
FuncVEP CTI	Benign	-	0.13
GPN-Star LLR	N/A	-	-4.6
GPN-Star score	N/A	-	4.6
LIST_S2	Benign	T	0.84
MetaRNN	Benign	T	0.0017
MetaSVM	Benign	T	-1.2
Mutation Taster	N/A	polymorphism (auto)	87/13
MutationAssessor	Uncertain	M	2.8
PhyloP100	Benign	-	2.5
popEVE	Benign	-	-3.8
PrimateAI	Benign	T	0.46
PROVEAN	Benign	N	-1.9
REVEL	Benign	-	0.16
Sift	Benign	T	0.51
Sift4G	Pathogenic	D	0.0
Varity_R	N/A	-	0.20
VESM-3B	Benign	-	-8.2

Showing 27 of 27 scores

Splicing Scores

Algorithm	Calibrated prediction	Prediction	Score
DS_AG_spliceai	Pathogenic	- Position offset: -2	0.73
Pangolin (max)	Pathogenic	-	0.53
Pangolin gain	Pathogenic	- Position offset: -2	0.53
SpliceAI score (max)	Pathogenic	- Details are displayed if max score is > 0.2	0.73

Showing 4 of 4 scores

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

dbSNP: rs2070600;

hg19: chr6-32151443;

COSMIC: COSV107496643;

COSMIC: COSV107496643;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar