rs2272239

Positions:

• chr2-74178740-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018221.5(MOB1A):​c.-66A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 929,788 control chromosomes in the GnomAD database, including 8,577 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.16 (2335 hom., cov: 31)
  • Exomes 𝑓: 0.11 (6242 hom.)
• Consequence: MOB1A NM_018221.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0860

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]

MOB1A (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MOB1A	NM_018221.5	c.-66A>C		5_prime_UTR_variant	1/6	ENST00000396049.5	NP_060691.2
MOB1A	NM_001317110.2	c.-66A>C		5_prime_UTR_variant	1/6		NP_001304039.1
MOB1A	NM_001317112.2	c.-66A>C		5_prime_UTR_variant	1/5		NP_001304041.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MOB1A	ENST00000396049.5	c.-66A>C		5_prime_UTR_variant	1/6	1	NM_018221.5	ENSP00000379364.3

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24506 AN: 151462 Hom.: 2327 Cov.: 31

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.381

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.0920

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.159

GnomAD4 exome AF: 0.112 AC: 87475 AN: 778206 Hom.: 6242 Cov.: 10 AF XY: 0.112 AC XY: 42429 AN XY: 377342

Gnomad4 AFR exome AF: 0.200

Gnomad4 AMR exome AF: 0.297

Gnomad4 ASJ exome AF: 0.110

Gnomad4 EAS exome AF: 0.337

Gnomad4 SAS exome AF: 0.125

Gnomad4 FIN exome AF: 0.0881

Gnomad4 NFE exome AF: 0.0992

Gnomad4 OTH exome AF: 0.128

GnomAD4 genome AF: 0.162 AC: 24539 AN: 151582 Hom.: 2335 Cov.: 31 AF XY: 0.164 AC XY: 12141 AN XY: 74070

Gnomad4 AFR AF: 0.211

Gnomad4 AMR AF: 0.253

Gnomad4 ASJ AF: 0.111

Gnomad4 EAS AF: 0.380

Gnomad4 SAS AF: 0.142

Gnomad4 FIN AF: 0.0920

Gnomad4 NFE AF: 0.111

Gnomad4 OTH AF: 0.159

Alfa AF: 0.138 Hom.: 248

Bravo AF: 0.183

Asia WGS AF: 0.232 AC: 808 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	10
DANN	Benign	0.68
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2272239; hg19: chr2-74405867; COSMIC: COSV68517453; COSMIC: COSV68517453;