chr6-32183666-C-A

Variant names:

• chr6-32183666-C-A
• rs2070600
• NM_001136.5:c.244G>T
• AGER p.Gly82Cys

GermlineCancer (beta)

Variant summary

Our verdict is Uncertain significance.

+1 Uncertain · Cold

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received 1 classification points (ACMG Germline Pathogenicity v2019). PM2BP4

The NM_001136.5(AGER):c.244G>T (p.Gly82Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant is absent from the gnomAD population database at sites with sufficient sequencing coverage. In-silico predictor (REVEL) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Other variants at the same amino acid position have been reported in ClinVar (not pathogenic): p.G82S: Uncertain_significance (ClinVar VariationId 2582841, 0 stars)

• Frequency: Genomes: not found (cov: 33)
• Consequence: AGER NM_001136.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.46
• Publications: 239 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

Classification was made for transcript:

Our verdict: Uncertain_significance. The variant received 1 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	PM2Absent/extremely low in population databases		Absent from gnomAD (AR/unknown gene) — PM2; Absent from gnomAD at well-covered site (MOI: unknown) (threshold 0.001) — PM2 moderate.
	BP4Computational evidence suggests no impact		Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Supporting).

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>T p.Gly82Cys	missense	Exon 3 of 11	Prot: NP_001127.1 UniProt:
	AGER NM_001206929.2		c.244G>T p.Gly82Cys	missense	Exon 3 of 11	Prot: NP_001193858.1 UniProt:
	AGER NM_001206932.2		c.202G>T p.Gly68Cys	missense	Exon 3 of 11	Prot: NP_001193861.1 UniProt:

AGER NM_001136.5

MANE Select

HGVSc / HGVSpc.244G>Tp.Gly82Cys

Exon rankExon 3 of 11

missense

Prot: NP_001127.1UniProt: Q15109-1

AGER NM_001206929.2

HGVSc / HGVSpc.244G>Tp.Gly82Cys

Exon rankExon 3 of 11

missense

Prot: NP_001193858.1UniProt: Q15109-6

AGER NM_001206932.2

HGVSc / HGVSpc.202G>Tp.Gly68Cys

Exon rankExon 3 of 11

missense

Prot: NP_001193861.1UniProt: Q15109-7

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	AGER ENST00000375076.9	TSL:1MANE Select	c.244G>T p.Gly82Cys	missense	Exon 3 of 11	Prot: ENSP00000364217.4 UniProt:
	AGER ENST00000375069.7	TSL:1	c.244G>T p.Gly82Cys	missense	Exon 3 of 11	Prot: ENSP00000364210.4 UniProt:
	AGER ENST00000438221.6	TSL:1	c.244G>T p.Gly82Cys	missense	Exon 3 of 10	Prot: ENSP00000387887.2 UniProt:

AGER ENST00000375076.9

TSL:1MANE Select

HGVSc / HGVSpc.244G>Tp.Gly82Cys

Exon rankExon 3 of 11

missense

Prot: ENSP00000364217.4UniProt: Q15109-1

AGER ENST00000375069.7

TSL:1

HGVSc / HGVSpc.244G>Tp.Gly82Cys

Exon rankExon 3 of 11

missense

Prot: ENSP00000364210.4UniProt: Q15109-6

AGER ENST00000438221.6

TSL:1

HGVSc / HGVSpc.244G>Tp.Gly82Cys

Exon rankExon 3 of 10

missense

Prot: ENSP00000387887.2UniProt: 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 3 sources Large-scale international reference populations
GnomAD3 genomes	AF:	AC:	Hom:	AN:	Cov:33
GnomAD4 exome	AF:	AC:	Hom:	AN:	Cov:36
GnomAD4 genome	AF:	AC:	Hom:	AN:	Cov:33

Showing 3 sources

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Pathogenic	27
AlphaMissense	Pathogenic	0.81
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.070
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Uncertain	0.90	D
FuncVEP CTI	Pathogenic	0.96
GPN-Star LLR	N/A	-7.4
GPN-Star score	N/A	7.4
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.61	D
MetaSVM	Benign	-1.2	T
Mutation Taster	N/A	73/27	polymorphism
MutationAssessor	Pathogenic	3.3	M
PhyloP100	Benign	2.5
popEVE	Benign	-3.8
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.28
Sift	Benign	0.12	T
Sift4G	Pathogenic	0.0	D
Varity_R	N/A	0.43
VESM-3B	Benign	-12

Showing 28 of 28 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.060
SpliceAI score (max)	Benign	0.12	Details are displayed if max score is > 0.2

Showing 2 of 2 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.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

dbSNP: rs2070600;

hg19: chr6-32151443;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar