chr15-96340092-G-T

Variant names:

• chr15-96340092-G-T
• rs11045
• NM_021005.4:c.*2470G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021005.4(NR2F2):​c.*2470G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 152,036 control chromosomes in the GnomAD database, including 19,996 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 0.44 (19996 hom., cov: 32)
  • Exomes 𝑓: 0.20 (0 hom.)
• Consequence: NR2F2 NM_021005.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.619
• Publications: 6 publications found

Genes affected

NR2F2 (HGNC:7976): (nuclear receptor subfamily 2 group F member 2) This gene encodes a member of the steroid thyroid hormone superfamily of nuclear receptors. The encoded protein is a ligand inducible transcription factor that is involved in the regulation of many different genes. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Mar 2010]

NR2F2 Gene-Disease associations (from GenCC):

• 46,xx sex reversal 5

  Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
• NR2F2 related multiple congenital anomalies/dysmorphic syndrome

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• congenital heart defects, multiple types, 4

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.82 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021005.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR2F2	NM_021005.4	MANE Select	c.*2470G>T		3_prime_UTR	Exon 3 of 3	NP_066285.1
	NR2F2	NM_001145155.2		c.*2470G>T		3_prime_UTR	Exon 3 of 3	NP_001138627.1
	NR2F2	NM_001145156.1		c.*2470G>T		3_prime_UTR	Exon 3 of 3	NP_001138628.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR2F2	ENST00000394166.8	TSL:1 MANE Select	c.*2470G>T		3_prime_UTR	Exon 3 of 3	ENSP00000377721.3
	NR2F2	ENST00000394171.6	TSL:2	c.*2470G>T		3_prime_UTR	Exon 3 of 3	ENSP00000377726.2

Frequencies

GnomAD3 genomes AF: 0.439 AC: 66656 AN: 151908 Hom.: 19923 Cov.: 32

Gnomad AFR AF: 0.827

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.459

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.717

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.405

GnomAD4 exome AF: 0.200 AC: 2 AN: 10 Hom.: 0 Cov.: 0 AF XY: 0.167 AC XY: 1 AN XY: 6

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.250 AC: 1 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.167 AC: 1 AN: 6

Other (OTH) AC: 0 AN: 0

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000000770867), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.439 AC: 66800 AN: 152026 Hom.: 19996 Cov.: 32 AF XY: 0.445 AC XY: 33032 AN XY: 74284

African (AFR) AF: 0.828 AC: 34338 AN: 41480

American (AMR) AF: 0.459 AC: 7026 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 658 AN: 3468

East Asian (EAS) AF: 0.717 AC: 3710 AN: 5172

South Asian (SAS) AF: 0.270 AC: 1297 AN: 4800

European-Finnish (FIN) AF: 0.323 AC: 3410 AN: 10548

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.225 AC: 15296 AN: 67944

Other (OTH) AF: 0.411 AC: 868 AN: 2112

Alfa AF: 0.307 Hom.: 17503

Bravo AF: 0.475

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	14
DANN	Benign	0.87
PhyloP100		0.62
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11045; hg19: chr15-96883321;