8-70361080-T-C

Variant names:

• chr8-70361080-T-C
• rs6472520
• NM_006540.4:c.-77+42620A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006540.4(NCOA2):​c.-77+42620A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.382 in 152,098 control chromosomes in the GnomAD database, including 13,671 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.38 (13671 hom., cov: 32)
• Consequence: NCOA2 NM_006540.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.136
• Publications: 4 publications found

Genes affected

NCOA2 (HGNC:7669): (nuclear receptor coactivator 2) The protein encoded by this gene functions as a transcriptional coactivator for nuclear hormone receptors, including steroid, thyroid, retinoid, and vitamin D receptors. The encoded protein acts as an intermediary factor for the ligand-dependent activity of these nuclear receptors, which regulate their target genes upon binding of cognate response elements. This gene has been found to be involved in translocations that result in fusions with other genes in various cancers, including the lysine acetyltransferase 6A (KAT6A) gene in acute myeloid leukemia, the ETS variant 6 (ETV6) gene in acute lymphoblastic leukemia, and the hes related family bHLH transcription factor with YRPW motif 1 (HEY1) gene in mesenchymal chondrosarcoma. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.681 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006540.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCOA2	NM_006540.4	MANE Select	c.-77+42620A>G		intron	N/A	NP_006531.1
	NCOA2	NM_001321703.2		c.-77+42946A>G		intron	N/A	NP_001308632.1
	NCOA2	NM_001321707.2		c.-77+42254A>G		intron	N/A	NP_001308636.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCOA2	ENST00000452400.7	TSL:1 MANE Select	c.-77+42620A>G		intron	N/A	ENSP00000399968.2
	NCOA2	ENST00000520416.1	TSL:3	c.-77+41083A>G		intron	N/A	ENSP00000430850.1
	NCOA2	ENST00000518287.6	TSL:5	n.-77+40734A>G		intron	N/A	ENSP00000430148.2

Frequencies

GnomAD3 genomes AF: 0.381 AC: 57926 AN: 151980 Hom.: 13620 Cov.: 32

Gnomad AFR AF: 0.635

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.699

Gnomad SAS AF: 0.478

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.347

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.382 AC: 58046 AN: 152098 Hom.: 13671 Cov.: 32 AF XY: 0.384 AC XY: 28585 AN XY: 74364

African (AFR) AF: 0.635 AC: 26328 AN: 41458

American (AMR) AF: 0.323 AC: 4942 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.264 AC: 917 AN: 3470

East Asian (EAS) AF: 0.700 AC: 3626 AN: 5182

South Asian (SAS) AF: 0.478 AC: 2304 AN: 4816

European-Finnish (FIN) AF: 0.255 AC: 2698 AN: 10576

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.237 AC: 16139 AN: 67988

Other (OTH) AF: 0.350 AC: 737 AN: 2106

Alfa AF: 0.284 Hom.: 3761

Bravo AF: 0.395

Asia WGS AF: 0.602 AC: 2087 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.3
DANN	Benign	0.71
PhyloP100		-0.14
Mutation Taster		=100/0	polymorphism (auto)

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: rs6472520; hg19: chr8-71273315;