rs11777228

Positions:

• chr8-70333055-G-A
• chr8-70333055-G-C

Variant summary

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

The NM_006540.4(NCOA2):​c.-76-36255C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0255 in 152,254 control chromosomes in the GnomAD database, including 75 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 0.026 (75 hom., cov: 32)
• Consequence: NCOA2 NM_006540.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0240

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=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0679 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCOA2	NM_006540.4	c.-76-36255C>T		intron_variant		ENST00000452400.7	NP_006531.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCOA2	ENST00000452400.7	c.-76-36255C>T		intron_variant		1	NM_006540.4	ENSP00000399968	P1
NCOA2	ENST00000520416.1	c.-76-36255C>T		intron_variant		3		ENSP00000430850
NCOA2	ENST00000518287.6	c.-76-36255C>T		intron_variant, NMD_transcript_variant		5		ENSP00000430148

Frequencies

GnomAD3 genomes AF: 0.0256 AC: 3894 AN: 152136 Hom.: 76 Cov.: 32

Gnomad AFR AF: 0.00594

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.0196

Gnomad ASJ AF: 0.0349

Gnomad EAS AF: 0.0408

Gnomad SAS AF: 0.0742

Gnomad FIN AF: 0.0339

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0322

Gnomad OTH AF: 0.0292

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

GnomAD4 genome AF: 0.0255 AC: 3889 AN: 152254 Hom.: 75 Cov.: 32 AF XY: 0.0266 AC XY: 1983 AN XY: 74444

Gnomad4 AFR AF: 0.00592

Gnomad4 AMR AF: 0.0196

Gnomad4 ASJ AF: 0.0349

Gnomad4 EAS AF: 0.0404

Gnomad4 SAS AF: 0.0742

Gnomad4 FIN AF: 0.0339

Gnomad4 NFE AF: 0.0322

Gnomad4 OTH AF: 0.0280

Alfa AF: 0.0185 Hom.: 11

Bravo AF: 0.0232

Asia WGS AF: 0.0560 AC: 193 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.7
DANN	Benign	0.61

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: rs11777228; hg19: chr8-71245290;