rs2926703

chr8-70254759-G-A

Variant summary

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

The NM_006540.4(NCOA2):c.-19-37995C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.757 in 151,386 control chromosomes in the GnomAD database, including 44,484 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 0.76 (44484 hom., cov: 27)
• Consequence: NCOA2 NM_006540.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.02

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.837 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NCOA2	NM_006540.4	c.-19-37995C>T		intron_variant		ENST00000452400.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NCOA2	ENST00000452400.7	c.-19-37995C>T		intron_variant		1	NM_006540.4	P1
NCOA2	ENST00000520416.1	c.-19-37995C>T		intron_variant		3
NCOA2	ENST00000518287.6	c.-19-37995C>T		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.757 AC: 114448 AN: 151270 Hom.: 44455 Cov.: 27

Gnomad AFR AF: 0.618

Gnomad AMI AF: 0.916

Gnomad AMR AF: 0.823

Gnomad ASJ AF: 0.790

Gnomad EAS AF: 0.430

Gnomad SAS AF: 0.597

Gnomad FIN AF: 0.847

Gnomad MID AF: 0.799

Gnomad NFE AF: 0.843

Gnomad OTH AF: 0.777

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

GnomAD4 genome AF: 0.757 AC: 114527 AN: 151386 Hom.: 44484 Cov.: 27 AF XY: 0.754 AC XY: 55738 AN XY: 73890

Gnomad4 AFR AF: 0.618

Gnomad4 AMR AF: 0.823

Gnomad4 ASJ AF: 0.790

Gnomad4 EAS AF: 0.430

Gnomad4 SAS AF: 0.596

Gnomad4 FIN AF: 0.847

Gnomad4 NFE AF: 0.843

Gnomad4 OTH AF: 0.777

Alfa AF: 0.807 Hom.: 21673

Bravo AF: 0.753

Asia WGS AF: 0.553 AC: 1929 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	15
Dann	Benign	0.71

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: rs2926703; hg19: chr8-71166994;