2-74159231-TAA-T

Variant names:

• chr2-74159231-TAA-T
• rs1558830933
• NM_018221.5:c.431_432delTT

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_018221.5(MOB1A):​c.431_432delTT​(p.Phe144TyrfsTer24) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MOB1A NM_018221.5 frameshift
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.29

Genes affected

MOB1A (HGNC:16015): (MOB kinase activator 1A) The protein encoded by this gene is a component of the Hippo signaling pathway, which controls organ size and tumor growth by enhancing apoptosis. Loss of the encoded protein results in cell proliferation and cancer formation. The encoded protein is also involved in the control of microtubule stability during cytokinesis. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2015]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MOB1A	NM_018221.5	c.431_432delTT	p.Phe144TyrfsTer24	frameshift_variant	Exon 5 of 6	ENST00000396049.5	NP_060691.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MOB1A	ENST00000396049.5	c.431_432delTT	p.Phe144TyrfsTer24	frameshift_variant	Exon 5 of 6	1	NM_018221.5	ENSP00000379364.3
MOB1A	ENST00000495286.5	n.617_618delTT		non_coding_transcript_exon_variant	Exon 5 of 5	3
MOB1A	ENST00000497054.5	n.620_621delTT		non_coding_transcript_exon_variant	Exon 5 of 5	2

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: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

May 18, 2017

Geisinger Autism and Developmental Medicine Institute, Geisinger Health System

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing;provider interpretation

This 9 year old female hypotonia, cerebral palsy, obesity, and periventricular leukomalacia carries a de novo frameshift variant in the MOB1A gene. This is a gene of uncertain significance; no known human disorders have been clearly associated with this gene. This variant is absent from the gnomAD database. -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1558830933; hg19: chr2-74386358;