chr2-238253086-CGGTGGGGAGGCCCTACCCATGGCCGAT-C
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 3P and 6B. PM4PP3BP6_ModerateBS2
The NM_022817.3(PER2):c.2910_2936del(p.Ser971_Pro979del) variant causes a inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000191 in 1,611,398 control chromosomes in the GnomAD database, including 3 homozygotes. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000085 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00020 ( 3 hom. )
Consequence
PER2
NM_022817.3 inframe_deletion
NM_022817.3 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 8.60
Genes affected
PER2 (HGNC:8846): (period circadian regulator 2) This gene is a member of the Period family of genes and is expressed in a circadian pattern in the suprachiasmatic nucleus, the primary circadian pacemaker in the mammalian brain. Genes in this family encode components of the circadian rhythms of locomotor activity, metabolism, and behavior. This gene is upregulated by CLOCK/ARNTL heterodimers but then represses this upregulation in a feedback loop using PER/CRY heterodimers to interact with CLOCK/ARNTL. Polymorphisms in this gene may increase the risk of getting certain cancers and have been linked to sleep disorders. [provided by RefSeq, Jan 2014]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PM4
?
Nonframeshift variant in NON repetitive region in NM_022817.3.
PP3
?
No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
BP6
?
Variant 2-238253086-CGGTGGGGAGGCCCTACCCATGGCCGAT-C is Benign according to our data. Variant chr2-238253086-CGGTGGGGAGGCCCTACCCATGGCCGAT-C is described in ClinVar as [Likely_benign]. Clinvar id is 3055231.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High AC in GnomAd at 14 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PER2 | NM_022817.3 | c.2910_2936del | p.Ser971_Pro979del | inframe_deletion | 19/23 | ENST00000254657.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PER2 | ENST00000254657.8 | c.2910_2936del | p.Ser971_Pro979del | inframe_deletion | 19/23 | 1 | NM_022817.3 | P1 | |
ENST00000456601.1 | n.1525-1094_1525-1068del | intron_variant, non_coding_transcript_variant | 2 | ||||||
PER2 | ENST00000707129.1 | c.2910_2936del | p.Ser971_Pro979del | inframe_deletion | 19/23 | P1 | |||
PER2 | ENST00000707130.1 | c.2910_2936del | p.Ser971_Pro979del | inframe_deletion | 19/23 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000921 AC: 14AN: 152090Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000392 AC: 98AN: 250248Hom.: 0 AF XY: 0.000517 AC XY: 70AN XY: 135380
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GnomAD4 exome AF: 0.000201 AC: 294AN: 1459190Hom.: 3 AF XY: 0.000280 AC XY: 203AN XY: 725376
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
PER2-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 01, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at