Genetic Variant NCOA2:c.3682-398C>T (chr8-70127445-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.233

Publications

0 publications found

Variant links:

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]

NCOA2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
NCOA2	NM_006540.4 link	c.3682-398C>T		intron_variant	Intron 18 of 22	ENST00000452400.7	NP_006531.1	Q15596

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
NCOA2	ENST00000452400.7 link	c.3682-398C>T	intron_variant	Intron 18 of 22	1	NM_006540.4	ENSP00000399968.2	Q15596
NCOA2	ENST00000518363.2 link	c.1057-398C>T	intron_variant	Intron 6 of 10	2		ENSP00000429132.2	H0YBB6
NCOA2	ENST00000518287.6 link	n.*639-398C>T	intron_variant	Intron 17 of 20	5		ENSP00000430148.2	E7EWM1
NCOA2	ENST00000521239.1 link	n.125-398C>T	intron_variant	Intron 2 of 2	4

Frequencies

GnomAD3 genomes

AF:

0.0223

AC:

3387

AN:

152142

Hom.:

115

Cov.:

show subpopulations

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.:

AF XY:

0.0239

AC XY:

1777

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.00556

AC:

231

AN:

41550

American (AMR)

AF:

0.0248

AC:

380

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0464

AC:

161

AN:

3472

East Asian (EAS)

AF:

0.162

AC:

841

AN:

5178

South Asian (SAS)

AF:

0.0831

AC:

400

AN:

4816

European-Finnish (FIN)

AF:

0.00641

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.0476

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0183

AC:

1243

AN:

68012

Other (OTH)

AF:

0.0213

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

170

340

509

679

849

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

150

200

250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0174

Hom.:

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

(source)

DANN

Benign

0.67

PhyloP100

0.23

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over