8-70197718-C-T

Variant names:

• chr8-70197718-C-T
• rs17675762
• NM_006540.4:c.259+16185G>A

Variant summary

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

The NM_006540.4(NCOA2):​c.259+16185G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0867 in 152,198 control chromosomes in the GnomAD database, including 724 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 0.087 (724 hom., cov: 33)
• Consequence: NCOA2 NM_006540.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.752
• Publications: 2 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=-0.76).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCOA2	NM_006540.4	c.259+16185G>A		intron_variant	Intron 4 of 22	ENST00000452400.7	NP_006531.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCOA2	ENST00000452400.7	c.259+16185G>A		intron_variant	Intron 4 of 22	1	NM_006540.4	ENSP00000399968.2
NCOA2	ENST00000518287.6	n.259+16185G>A		intron_variant	Intron 4 of 20	5		ENSP00000430148.2

Frequencies

GnomAD3 genomes AF: 0.0868 AC: 13195 AN: 152080 Hom.: 724 Cov.: 33

Gnomad AFR AF: 0.0299

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.0777

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.000576

Gnomad SAS AF: 0.0338

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.104

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

GnomAD4 genome AF: 0.0867 AC: 13197 AN: 152198 Hom.: 724 Cov.: 33 AF XY: 0.0846 AC XY: 6297 AN XY: 74398

African (AFR) AF: 0.0299 AC: 1240 AN: 41532

American (AMR) AF: 0.0776 AC: 1187 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 355 AN: 3472

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5194

South Asian (SAS) AF: 0.0341 AC: 164 AN: 4814

European-Finnish (FIN) AF: 0.103 AC: 1093 AN: 10576

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.129 AC: 8758 AN: 67994

Other (OTH) AF: 0.103 AC: 218 AN: 2114

Alfa AF: 0.102 Hom.: 123

Bravo AF: 0.0851

Asia WGS AF: 0.0160 AC: 55 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	7.3
DANN	Benign	0.65
PhyloP100		0.75
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: rs17675762; hg19: chr8-71109953;