chr15-96332196-GGCCCGCC-G

Position:

• chr15-96332196-GGCCCGCC-G

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_Strong PM2 PP5

The NM_021005.4(NR2F2):​c.97_103delCCGCCCG​(p.Pro33fs) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 31)
• Consequence: NR2F2 NM_021005.4 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:2
• Conservation: PhyloP100: 5.51

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 Likely_pathogenic. Variant got 7 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 5 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 15-96332196-GGCCCGCC-G is Pathogenic according to our data. Variant chr15-96332196-GGCCCGCC-G is described in ClinVar as [Pathogenic]. Clinvar id is 916034.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr15-96332196-GGCCCGCC-G is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NR2F2	NM_021005.4	c.97_103delCCGCCCG	p.Pro33fs	frameshift_variant	1/3	ENST00000394166.8	NP_066285.1
NR2F2	NM_001145155.2	c.44-1874_44-1868delCCGCCCG		intron_variant			NP_001138627.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NR2F2	ENST00000394166.8	c.97_103delCCGCCCG	p.Pro33fs	frameshift_variant	1/3	1	NM_021005.4	ENSP00000377721.3
NR2F2	ENST00000421109.6	c.44-1874_44-1868delCCGCCCG		intron_variant		1		ENSP00000401674.2

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: Pathogenic

Submissions summary: Pathogenic:2

Revision: no assertion criteria provided

Submissions by phenotype

46,xx sex reversal 5 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jun 02, 2020

- -

Congenital heart defects, multiple types, 4 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jun 02, 2020

- -

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: rs1899167019; hg19: chr15-96875425;