chr22-50276655-TCATGTCCTGGTCGCTGACCTGCACCATCTGCCGGATCCCCTTGTAGTAACTGCAGGGGTGGGAGCATCATACAGTGTGGGCGGCAGGGACCACAAAGGGGGTGGTGGGGGAAACCAAGGCCTGAACCTCCCCGCAGGGGGTCGAGGGTGGGCATGGGGGCCTGGCCTGGAGGGCAGGCAGACTTACTCCTCCACCATCTTCTTGTAGGTGGAGATCTCCTTGGCGTACAGCAGCTTGTTGCTGGGAGAATCCTGTTGGGGACAAAACCCAGTGATGCCTGGCCAAGGGGGCCAGGCTGGGGCTGCTCAGAGTACCCCTGGGTAGCTTCCCCTGCCCCGAACTCCTGACACTTTCATCAAGAAAACTATGGGCCGGGCGCAGTGGCTCAGGCCTGTAATCCTAGCACTTTGGGAGGCTGAGGCAGGCAGATCACCTGAGGTCAGGGGTTCGAGACCAGCCTGCCCAACATGGTGAAACCCCGTCTCTACTAAAAATACTAGCCGTGCGTTGTGGCACATGCCTGTAGTCCCAGCTACTCAGGAGGCAGCGGCGGGAAAATCGCTTGAACCTAGAAGGCGGAGGTTGCAG-T

Variant names:

• chr22-50276655-TCATGTCCTGGTCGCTGACCTGCACCATCTGCCGGATCCCCTTGTAGTAACTGCAGGGGTGGGAGCATCATACAGTGTGGGCGGCAGGGACCACAAAGGGGGTGGTGGGGGAAACCAAGGCCTGAACCTCCCCGCAGGGGGTCGAGGGTGGGCATGGGGGCCTGGCCTGGAGGGCAGGCAGACTTACTCCTCCACCATCTTCTTGTAGGTGGAGATCTCCTTGGCGTACAGCAGCTTGTTGCTGGGAGAATCCTGTTGGGGACAAAACCCAGTGATGCCTGGCCAAGGGGGCCAGGCTGGGGCTGCTCAGAGTACCCCTGGGTAGCTTCCCCTGCCCCGAACTCCTGACACTTTCATCAAGAAAACTATGGGCCGGGCGCAGTGGCTCAGGCCTGTAATCCTAGCACTTTGGGAGGCTGAGGCAGGCAGATCACCTGAGGTCAGGGGTTCGAGACCAGCCTGCCCAACATGGTGAAACCCCGTCTCTACTAAAAATACTAGCCGTGCGTTGTGGCACATGCCTGTAGTCCCAGCTACTCAGGAGGCAGCGGCGGGAAAATCGCTTGAACCTAGAAGGCGGAGGTTGCAG-T
• NM_012401.4:c.5197-337_5310del

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM4 PP3 PP5

The NM_012401.4(PLXNB2):​c.5197-337_5310del​(p.Asp1733_Met1770del) variant causes a conservative inframe deletion change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PLXNB2 NM_012401.4 conservative_inframe_deletion
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.70
• Publications: 1 publications found

Genes affected

PLXNB2 (HGNC:9104): (plexin B2) Members of the B class of plexins, such as PLXNB2 are transmembrane receptors that participate in axon guidance and cell migration in response to semaphorins (Perrot et al. (2002) [PubMed 12183458]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_012401.4.
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
• PP5: Variant 22-50276655-TCATGTCCTGGTCGCTGACCTGCACCATCTGCCGGATCCCCTTGTAGTAACTGCAGGGGTGGGAGCATCATACAGTGTGGGCGGCAGGGACCACAAAGGGGGTGGTGGGGGAAACCAAGGCCTGAACCTCCCCGCAGGGGGTCGAGGGTGGGCATGGGGGCCTGGCCTGGAGGGCAGGCAGACTTACTCCTCCACCATCTTCTTGTAGGTGGAGATCTCCTTGGCGTACAGCAGCTTGTTGCTGGGAGAATCCTGTTGGGGACAAAACCCAGTGATGCCTGGCCAAGGGGGCCAGGCTGGGGCTGCTCAGAGTACCCCTGGGTAGCTTCCCCTGCCCCGAACTCCTGACACTTTCATCAAGAAAACTATGGGCCGGGCGCAGTGGCTCAGGCCTGTAATCCTAGCACTTTGGGAGGCTGAGGCAGGCAGATCACCTGAGGTCAGGGGTTCGAGACCAGCCTGCCCAACATGGTGAAACCCCGTCTCTACTAAAAATACTAGCCGTGCGTTGTGGCACATGCCTGTAGTCCCAGCTACTCAGGAGGCAGCGGCGGGAAAATCGCTTGAACCTAGAAGGCGGAGGTTGCAG-T is Pathogenic according to our data. Variant chr22-50276655-TCATGTCCTGGTCGCTGACCTGCACCATCTGCCGGATCCCCTTGTAGTAACTGCAGGGGTGGGAGCATCATACAGTGTGGGCGGCAGGGACCACAAAGGGGGTGGTGGGGGAAACCAAGGCCTGAACCTCCCCGCAGGGGGTCGAGGGTGGGCATGGGGGCCTGGCCTGGAGGGCAGGCAGACTTACTCCTCCACCATCTTCTTGTAGGTGGAGATCTCCTTGGCGTACAGCAGCTTGTTGCTGGGAGAATCCTGTTGGGGACAAAACCCAGTGATGCCTGGCCAAGGGGGCCAGGCTGGGGCTGCTCAGAGTACCCCTGGGTAGCTTCCCCTGCCCCGAACTCCTGACACTTTCATCAAGAAAACTATGGGCCGGGCGCAGTGGCTCAGGCCTGTAATCCTAGCACTTTGGGAGGCTGAGGCAGGCAGATCACCTGAGGTCAGGGGTTCGAGACCAGCCTGCCCAACATGGTGAAACCCCGTCTCTACTAAAAATACTAGCCGTGCGTTGTGGCACATGCCTGTAGTCCCAGCTACTCAGGAGGCAGCGGCGGGAAAATCGCTTGAACCTAGAAGGCGGAGGTTGCAG-T is described in ClinVar as [Pathogenic]. Clinvar id is 1895427.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLXNB2	NM_012401.4	c.5197-337_5310del	p.Asp1733_Met1770del	conservative_inframe_deletion	Exon 34 of 37	ENST00000359337.9	NP_036533.2
PLXNB2	NM_012401.4	c.5197-337_5310del		exon_loss_variant	Exon 34 of 37	ENST00000359337.9	NP_036533.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLXNB2	ENST00000359337.9	c.5197-337_5310del	p.Asp1733_Met1770del	conservative_inframe_deletion	Exon 35 of 37	5	NM_012401.4	ENSP00000352288.4
PLXNB2	ENST00000359337.9	c.5197-337_5310del		exon_loss_variant	Exon 34 of 37	5	NM_012401.4	ENSP00000352288.4

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

See cases Pathogenic:1

Jan 04, 2023

Leeds Amelogenesis Imperfecta Research Group, University of Leeds

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: research

Variant not indentified in Conrad et al. catalogue of CNVs -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.7

Splicing

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

Other links and lift over

hg19: chr22-50715084;