chr15-96332202-CCGCCCGG-C

Position:

• chr15-96332202-CCGCCCGG-C

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_021005.4(NR2F2):​c.103_109del​(p.Gly35ArgfsTer75) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: NR2F2 NM_021005.4 frameshift
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:2
• Conservation: PhyloP100: 6.90

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]

ACMG classification

Verdict is Pathogenic. Variant got 12 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 20 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 15-96332202-CCGCCCGG-C is Pathogenic according to our data. Variant chr15-96332202-CCGCCCGG-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 916038.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-96332202-CCGCCCGG-C is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NR2F2	NM_021005.4	c.103_109del	p.Gly35ArgfsTer75	frameshift_variant	1/3	ENST00000394166.8
NR2F2	NM_001145155.2	c.44-1868_44-1862del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NR2F2	ENST00000394166.8	c.103_109del	p.Gly35ArgfsTer75	frameshift_variant	1/3	1	NM_021005.4	P1
NR2F2	ENST00000421109.6	c.44-1868_44-1862del		intron_variant		1

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

Submissions by phenotype

46,xx sex reversal 5 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jun 02, 2020

- -

not provided Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Revvity Omics, Revvity

Dec 05, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1899167400; hg19: chr15-96875431;