rs10504467

Positions:

• chr8-70127445-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.3682-398C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0222 in 152,260 control chromosomes in the GnomAD database, including 115 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 0.022 (115 hom., cov: 32)
• Consequence: NCOA2 NM_006540.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.233

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NCOA2	NM_006540.4	c.3682-398C>T		intron_variant		ENST00000452400.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NCOA2	ENST00000452400.7	c.3682-398C>T		intron_variant		1	NM_006540.4	P1
NCOA2	ENST00000518363.2	c.1058-398C>T		intron_variant		2
NCOA2	ENST00000518287.6	c.*639-398C>T		intron_variant, NMD_transcript_variant		5
NCOA2	ENST00000521239.1	n.125-398C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0223 AC: 3387 AN: 152142 Hom.: 115 Cov.: 32

Gnomad AFR AF: 0.00560

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0248

Gnomad ASJ AF: 0.0464

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.0832

Gnomad FIN AF: 0.00641

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0183

Gnomad OTH AF: 0.0211

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

GnomAD4 genome AF: 0.0222 AC: 3384 AN: 152260 Hom.: 115 Cov.: 32 AF XY: 0.0239 AC XY: 1777 AN XY: 74458

Gnomad4 AFR AF: 0.00556

Gnomad4 AMR AF: 0.0248

Gnomad4 ASJ AF: 0.0464

Gnomad4 EAS AF: 0.162

Gnomad4 SAS AF: 0.0831

Gnomad4 FIN AF: 0.00641

Gnomad4 NFE AF: 0.0183

Gnomad4 OTH AF: 0.0213

Alfa AF: 0.0174 Hom.: 8

Bravo AF: 0.0217

Asia WGS AF: 0.103 AC: 358 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.6
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: rs10504467; hg19: chr8-71039680;