3-71772559-TAAAAA-T

Variant names:

• chr3-71772559-TAAAAA-T
• rs56679628
• NM_001126128.2:c.*160_*164delTTTTT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001126128.2(PROK2):​c.*160_*164delTTTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000431 in 464,510 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.0000043 (0 hom.)
• Consequence: PROK2 NM_001126128.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.18
• Publications: 0 publications found

Genes affected

PROK2 (HGNC:18455): (prokineticin 2) This gene encodes a protein expressed in the suprachiasmatic nucleus (SCN) circadian clock that may function as the output component of the circadian clock. The secreted form of the encoded protein may also serve as a chemoattractant for neuronal precursor cells in the olfactory bulb. Proteins from other vertebrates which are similar to this gene product were isolated based on homology to snake venom and secretions from frog skin, and have been shown to have diverse functions. Mutations in this gene are associated with Kallmann syndrome 4. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

PROK2 Gene-Disease associations (from GenCC):

• hypogonadotropic hypogonadism 4 with or without anosmia

  Inheritance: AR, SD, AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen
• hypogonadotropic hypogonadism

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Kallmann syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001126128.2. 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
	PROK2	NM_001126128.2	MANE Select	c.*160_*164delTTTTT		3_prime_UTR	Exon 4 of 4	NP_001119600.1	Q9HC23-1
	PROK2	NM_021935.4		c.*160_*164delTTTTT		3_prime_UTR	Exon 3 of 3	NP_068754.1	Q9HC23-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PROK2	ENST00000295619.4	TSL:1 MANE Select	c.*160_*164delTTTTT		3_prime_UTR	Exon 4 of 4	ENSP00000295619.3	Q9HC23-1
	PROK2	ENST00000353065.7	TSL:1	c.*160_*164delTTTTT		3_prime_UTR	Exon 3 of 3	ENSP00000295618.3	Q9HC23-2

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 0.00000431 AC: 2 AN: 464510 Hom.: 0 AF XY: 0.00000813 AC XY: 2 AN XY: 246006

African (AFR) AF: 0.00 AC: 0 AN: 12286

American (AMR) AF: 0.00 AC: 0 AN: 16736

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13448

East Asian (EAS) AF: 0.00 AC: 0 AN: 28910

South Asian (SAS) AF: 0.00 AC: 0 AN: 42274

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36934

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2222

European-Non Finnish (NFE) AF: 0.00000699 AC: 2 AN: 286188

Other (OTH) AF: 0.00 AC: 0 AN: 25512

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.2

Splicing

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

Other links and lift over

dbSNP: rs56679628; hg19: chr3-71821710;