rs7818867

Positions:

• chr8-70211699-T-C

Variant summary

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

The NM_006540.4(NCOA2):​c.259+2204A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0848 in 152,276 control chromosomes in the GnomAD database, including 691 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 0.085 (691 hom., cov: 31)
• Consequence: NCOA2 NM_006540.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.334

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=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCOA2	NM_006540.4	c.259+2204A>G		intron_variant		ENST00000452400.7	NP_006531.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCOA2	ENST00000452400.7	c.259+2204A>G		intron_variant		1	NM_006540.4	ENSP00000399968	P1
NCOA2	ENST00000518287.6	c.259+2204A>G		intron_variant, NMD_transcript_variant		5		ENSP00000430148

Frequencies

GnomAD3 genomes AF: 0.0848 AC: 12906 AN: 152158 Hom.: 692 Cov.: 31

Gnomad AFR AF: 0.0307

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.0755

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0342

Gnomad FIN AF: 0.0998

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.102

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

GnomAD4 genome AF: 0.0848 AC: 12909 AN: 152276 Hom.: 691 Cov.: 31 AF XY: 0.0828 AC XY: 6168 AN XY: 74450

Gnomad4 AFR AF: 0.0307

Gnomad4 AMR AF: 0.0754

Gnomad4 ASJ AF: 0.102

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0344

Gnomad4 FIN AF: 0.0998

Gnomad4 NFE AF: 0.125

Gnomad4 OTH AF: 0.100

Alfa AF: 0.0901 Hom.: 103

Bravo AF: 0.0834

Asia WGS AF: 0.0150 AC: 54 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.5
DANN	Benign	0.75

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: rs7818867; hg19: chr8-71123934;