12-1780869-ATTTT-ATTTTTT

Variant names:

• chr12-1780869-A-ATT
• rs745813254
• NM_024551.3:c.651-11_651-10dupTT

Variant summary

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

The NM_024551.3(ADIPOR2):​c.651-11_651-10dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000678 in 1,328,386 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: ADIPOR2 NM_024551.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0490
• Publications: 0 publications found

Genes affected

ADIPOR2 (HGNC:24041): (adiponectin receptor 2) The adiponectin receptors, ADIPOR1 (MIM 607945) and ADIPOR2, serve as receptors for globular and full-length adiponectin (MIM 605441) and mediate increased AMPK (see MIM 602739) and PPAR-alpha (PPARA; MIM 170998) ligand activities, as well as fatty acid oxidation and glucose uptake by adiponectin (Yamauchi et al., 2003 [PubMed 12802337]).[supplied by OMIM, Mar 2008]

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024551.3. 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
	ADIPOR2	NM_024551.3	MANE Select	c.651-11_651-10dupTT		intron	N/A	NP_078827.2
	ADIPOR2	NM_001375363.1		c.651-11_651-10dupTT		intron	N/A	NP_001362292.1
	ADIPOR2	NM_001375364.1		c.651-11_651-10dupTT		intron	N/A	NP_001362293.1	Q86V24

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADIPOR2	ENST00000357103.5	TSL:1 MANE Select	c.651-20_651-19insTT		intron	N/A	ENSP00000349616.4	Q86V24
	ADIPOR2	ENST00000878990.1		c.729-20_729-19insTT		intron	N/A	ENSP00000549049.1
	ADIPOR2	ENST00000878964.1		c.651-20_651-19insTT		intron	N/A	ENSP00000549023.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000350 AC: 5 AN: 142944 AF XY: 0.0000392

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000128

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000423

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000678 AC: 9 AN: 1328386 Hom.: 0 Cov.: 30 AF XY: 0.00000759 AC XY: 5 AN XY: 658498

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 28792

American (AMR) AF: 0.0000313 AC: 1 AN: 31956

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22124

East Asian (EAS) AF: 0.00 AC: 0 AN: 36266

South Asian (SAS) AF: 0.0000139 AC: 1 AN: 71844

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48942

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5216

European-Non Finnish (NFE) AF: 0.00000680 AC: 7 AN: 1028752

Other (OTH) AF: 0.00 AC: 0 AN: 54494

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.049
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs745813254; hg19: chr12-1890035;