chr8-70227095-T-G

Position:

• chr8-70227095-T-G

Variant summary

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

The NM_006540.4(NCOA2):​c.-19-10331A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0945 in 152,286 control chromosomes in the GnomAD database, including 947 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 0.095 (947 hom., cov: 32)
• Consequence: NCOA2 NM_006540.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.103

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 = 0.135 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCOA2	NM_006540.4	c.-19-10331A>C		intron_variant		ENST00000452400.7	NP_006531.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCOA2	ENST00000452400.7	c.-19-10331A>C		intron_variant		1	NM_006540.4	ENSP00000399968	P1
NCOA2	ENST00000519724.1	c.-19-10331A>C		intron_variant		4		ENSP00000430348
NCOA2	ENST00000520416.1	c.-19-10331A>C		intron_variant		3		ENSP00000430850
NCOA2	ENST00000518287.6	c.-19-10331A>C		intron_variant, NMD_transcript_variant		5		ENSP00000430148

Frequencies

GnomAD3 genomes AF: 0.0947 AC: 14403 AN: 152168 Hom.: 948 Cov.: 32

Gnomad AFR AF: 0.0237

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.0958

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.0604

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.109

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

GnomAD4 genome AF: 0.0945 AC: 14396 AN: 152286 Hom.: 947 Cov.: 32 AF XY: 0.0917 AC XY: 6827 AN XY: 74446

Gnomad4 AFR AF: 0.0236

Gnomad4 AMR AF: 0.0956

Gnomad4 ASJ AF: 0.204

Gnomad4 EAS AF: 0.000965

Gnomad4 SAS AF: 0.0605

Gnomad4 FIN AF: 0.118

Gnomad4 NFE AF: 0.138

Gnomad4 OTH AF: 0.107

Alfa AF: 0.117 Hom.: 171

Bravo AF: 0.0887

Asia WGS AF: 0.0310 AC: 107 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	0.093
DANN	Benign	0.39

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: rs72663955; hg19: chr8-71139330;