chr12-1780869-A-AT

Variant names:

• chr12-1780869-A-AT
• rs745813254
• NM_024551.3:c.651-10dupT

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP6 BS2

The NM_024551.3(ADIPOR2):​c.651-10dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00227 in 1,447,884 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00035 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0025 (0 hom.)
• Consequence: ADIPOR2 NM_024551.3 intron
• Clinical Significance: Likely benign no assertion criteria provided B:1
• 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: Likely_benign. The variant received -5 ACMG points.

• BP6: Variant 12-1780869-A-AT is Benign according to our data. Variant chr12-1780869-A-AT is described in ClinVar as Likely_benign. ClinVar VariationId is 3056279.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High AC in GnomAd4 at 53 AD gene.

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.651-10dupT		intron	N/A	NP_078827.2
	ADIPOR2	NM_001375363.1		c.651-10dupT		intron	N/A	NP_001362292.1
	ADIPOR2	NM_001375364.1		c.651-10dupT		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_651-19insT		intron	N/A	ENSP00000349616.4	Q86V24
	ADIPOR2	ENST00000878990.1		c.729-20_729-19insT		intron	N/A	ENSP00000549049.1
	ADIPOR2	ENST00000878964.1		c.651-20_651-19insT		intron	N/A	ENSP00000549023.1

Frequencies

GnomAD3 genomes AF: 0.000347 AC: 52 AN: 149808 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000295

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000598

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000584

Gnomad SAS AF: 0.000424

Gnomad FIN AF: 0.0000978

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000357

Gnomad OTH AF: 0.000492

GnomAD2 exomes AF: 0.00680 AC: 972 AN: 142944 AF XY: 0.00680

Gnomad AFR exome AF: 0.00590

Gnomad AMR exome AF: 0.0108

Gnomad ASJ exome AF: 0.0139

Gnomad EAS exome AF: 0.00730

Gnomad FIN exome AF: 0.00411

Gnomad NFE exome AF: 0.00532

Gnomad OTH exome AF: 0.00784

GnomAD4 exome AF: 0.00249 AC: 3235 AN: 1297966 Hom.: 0 Cov.: 30 AF XY: 0.00254 AC XY: 1637 AN XY: 643470

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

African (AFR) AF: 0.00316 AC: 89 AN: 28194

American (AMR) AF: 0.00587 AC: 185 AN: 31510

Ashkenazi Jewish (ASJ) AF: 0.00371 AC: 80 AN: 21582

East Asian (EAS) AF: 0.00275 AC: 98 AN: 35590

South Asian (SAS) AF: 0.00563 AC: 394 AN: 69924

European-Finnish (FIN) AF: 0.00278 AC: 133 AN: 47926

Middle Eastern (MID) AF: 0.000978 AC: 5 AN: 5112

European-Non Finnish (NFE) AF: 0.00213 AC: 2145 AN: 1004874

Other (OTH) AF: 0.00199 AC: 106 AN: 53254

⚠️ 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 AF: 0.000354 AC: 53 AN: 149918 Hom.: 0 Cov.: 32 AF XY: 0.000369 AC XY: 27 AN XY: 73142

African (AFR) AF: 0.000318 AC: 13 AN: 40824

American (AMR) AF: 0.000597 AC: 9 AN: 15076

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3450

East Asian (EAS) AF: 0.000586 AC: 3 AN: 5120

South Asian (SAS) AF: 0.000424 AC: 2 AN: 4712

European-Finnish (FIN) AF: 0.0000978 AC: 1 AN: 10220

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000357 AC: 24 AN: 67256

Other (OTH) AF: 0.000487 AC: 1 AN: 2054

Alfa AF: 0.00878 Hom.: 0

Bravo AF: 0.000332

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	ADIPOR2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

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

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs745813254; hg19: chr12-1890035; COSMIC: COSV63947285; COSMIC: COSV63947285;