rs1531362

chr8-70240960-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.-19-24196C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.051 in 152,166 control chromosomes in the GnomAD database, including 253 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 0.051 (253 hom., cov: 32)
• Consequence: NCOA2 NM_006540.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.339

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 (NFE) allele frequency at 95% confidence interval = 0.0744 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NCOA2	NM_006540.4	c.-19-24196C>T		intron_variant		ENST00000452400.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NCOA2	ENST00000452400.7	c.-19-24196C>T		intron_variant		1	NM_006540.4	P1
NCOA2	ENST00000519724.1	c.-20+4047C>T		intron_variant		4
NCOA2	ENST00000520416.1	c.-19-24196C>T		intron_variant		3
NCOA2	ENST00000518287.6	c.-19-24196C>T		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0510 AC: 7760 AN: 152048 Hom.: 253 Cov.: 32

Gnomad AFR AF: 0.0139

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.0500

Gnomad ASJ AF: 0.0536

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0286

Gnomad FIN AF: 0.0602

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0762

Gnomad OTH AF: 0.0684

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

GnomAD4 genome AF: 0.0510 AC: 7759 AN: 152166 Hom.: 253 Cov.: 32 AF XY: 0.0495 AC XY: 3685 AN XY: 74392

Gnomad4 AFR AF: 0.0138

Gnomad4 AMR AF: 0.0500

Gnomad4 ASJ AF: 0.0536

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0287

Gnomad4 FIN AF: 0.0602

Gnomad4 NFE AF: 0.0762

Gnomad4 OTH AF: 0.0676

Alfa AF: 0.0734 Hom.: 558

Bravo AF: 0.0506

Asia WGS AF: 0.00982 AC: 34 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	2.2
Dann	Benign	0.62

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: rs1531362; hg19: chr8-71153195;