8-70255759-C-T

Position:

• chr8-70255759-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006540.4(NCOA2):​c.-19-38995G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.88 in 152,220 control chromosomes in the GnomAD database, including 59,434 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 0.88 (59434 hom., cov: 32)
• Consequence: NCOA2 NM_006540.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.48

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.94 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCOA2	NM_006540.4	c.-19-38995G>A		intron_variant		ENST00000452400.7	NP_006531.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCOA2	ENST00000452400.7	c.-19-38995G>A		intron_variant		1	NM_006540.4	ENSP00000399968.2
NCOA2	ENST00000520416.1	c.-19-38995G>A		intron_variant		3		ENSP00000430850.1
NCOA2	ENST00000518287.6	n.-19-38995G>A		intron_variant		5		ENSP00000430148.2

Frequencies

GnomAD3 genomes AF: 0.880 AC: 133907 AN: 152102 Hom.: 59377 Cov.: 32

Gnomad AFR AF: 0.948

Gnomad AMI AF: 0.893

Gnomad AMR AF: 0.894

Gnomad ASJ AF: 0.895

Gnomad EAS AF: 0.592

Gnomad SAS AF: 0.687

Gnomad FIN AF: 0.866

Gnomad MID AF: 0.877

Gnomad NFE AF: 0.874

Gnomad OTH AF: 0.884

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

GnomAD4 genome AF: 0.880 AC: 134019 AN: 152220 Hom.: 59434 Cov.: 32 AF XY: 0.877 AC XY: 65261 AN XY: 74412

Gnomad4 AFR AF: 0.948

Gnomad4 AMR AF: 0.893

Gnomad4 ASJ AF: 0.895

Gnomad4 EAS AF: 0.592

Gnomad4 SAS AF: 0.686

Gnomad4 FIN AF: 0.866

Gnomad4 NFE AF: 0.873

Gnomad4 OTH AF: 0.884

Alfa AF: 0.870 Hom.: 76887

Bravo AF: 0.889

Asia WGS AF: 0.682 AC: 2373 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.0020
DANN	Benign	0.67

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

Publications

LitVar

Other links and lift over

dbSNP: rs2926702; hg19: chr8-71167994;