NM_001136.5:c.244_246delGGCinsTCG

Variant names:

• chr6-32183664-GCC-CGA
• NM_001136.5:c.244_246delGGCinsTCG
• AGER p.Gly82Ser

GermlineCancer (beta)

Variant summary

Our verdict is Uncertain significance.

+2 Uncertain · Warm

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received 2 classification points (ACMG Germline Pathogenicity v2019). PM2

The NM_001136.5(AGER):c.244_246delGGCinsTCG (p.Gly82Ser) variant causes a missense change. Note: allele frequency estimates from gnomAD may be inaccurate for this variant type (MNP or indel longer than 3 bp) due to technology limitations. The variant is absent from the gnomAD population database at sites with sufficient sequencing coverage. 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) 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: not found (cov: 33)
• Consequence: AGER NM_001136.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.89
• Publications: 0 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 2 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.

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.244_246delGGCinsTCG p.Gly82Ser	missense	N/A	Prot: NP_001127.1 UniProt:
	AGER NM_001206929.2		c.244_246delGGCinsTCG p.Gly82Ser	missense	N/A	Prot: NP_001193858.1 UniProt:
	AGER NM_001206932.2		c.202_204delGGCinsTCG p.Gly68Ser	missense	N/A	Prot: NP_001193861.1 UniProt:

AGER NM_001136.5

MANE Select

HGVSc / HGVSpc.244_246delGGCinsTCGp.Gly82Ser

Exon rankN/A

missense

Prot: NP_001127.1UniProt: Q15109-1

AGER NM_001206929.2

HGVSc / HGVSpc.244_246delGGCinsTCGp.Gly82Ser

Exon rankN/A

missense

Prot: NP_001193858.1UniProt: Q15109-6

AGER NM_001206932.2

HGVSc / HGVSpc.202_204delGGCinsTCGp.Gly68Ser

Exon rankN/A

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.244_246delGGCinsTCG p.Gly82Ser	missense	N/A	Prot: ENSP00000364217.4 UniProt:
	AGER ENST00000375069.7	TSL:1	c.244_246delGGCinsTCG p.Gly82Ser	missense	N/A	Prot: ENSP00000364210.4 UniProt:
	AGER ENST00000438221.6	TSL:1	c.244_246delGGCinsTCG p.Gly82Ser	missense	N/A	Prot: ENSP00000387887.2 UniProt:

AGER ENST00000375076.9

TSL:1MANE Select

HGVSc / HGVSpc.244_246delGGCinsTCGp.Gly82Ser

Exon rankN/A

missense

Prot: ENSP00000364217.4UniProt: Q15109-1

AGER ENST00000375069.7

TSL:1

HGVSc / HGVSpc.244_246delGGCinsTCGp.Gly82Ser

Exon rankN/A

missense

Prot: ENSP00000364210.4UniProt: Q15109-6

AGER ENST00000438221.6

TSL:1

HGVSc / HGVSpc.244_246delGGCinsTCGp.Gly82Ser

Exon rankN/A

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 2 sources Large-scale international reference populations
GnomAD3 genomes	AF:	AC:	Hom:	AN:	Cov:33
GnomAD4 genome	AF:	AC:	Hom:	AN:	Cov:33

Showing 2 sources

Tested, but no data found:GnomAD4 exomeIf GnomAD4 is missing, the position is probably not covered by the project.

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
PhyloP100	Uncertain	3.9

Showing 1 of 1 scores

Splicing Scores

No splicing scores have been computed for this variant.

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

hg19: chr6-32151441;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar