2-74165813-C-T

Variant names:

• chr2-74165813-C-T
• rs11126426
• NM_018221.5:c.276-462G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018221.5(MOB1A):​c.276-462G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.538 in 152,064 control chromosomes in the GnomAD database, including 24,176 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 0.54 (24176 hom., cov: 33)
• Consequence: MOB1A NM_018221.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.820
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.747 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MOB1A	NM_018221.5	c.276-462G>A		intron_variant	Intron 3 of 5	ENST00000396049.5	NP_060691.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MOB1A	ENST00000396049.5	c.276-462G>A		intron_variant	Intron 3 of 5	1	NM_018221.5	ENSP00000379364.3
MOB1A	ENST00000463975.1	n.470-462G>A		intron_variant	Intron 3 of 3	2
MOB1A	ENST00000495286.5	n.462-462G>A		intron_variant	Intron 3 of 4	3
MOB1A	ENST00000497054.5	n.465-462G>A		intron_variant	Intron 3 of 4	2

Frequencies

GnomAD3 genomes AF: 0.538 AC: 81747 AN: 151946 Hom.: 24133 Cov.: 33

Gnomad AFR AF: 0.742

Gnomad AMI AF: 0.490

Gnomad AMR AF: 0.577

Gnomad ASJ AF: 0.494

Gnomad EAS AF: 0.767

Gnomad SAS AF: 0.739

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.415

Gnomad OTH AF: 0.535

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

GnomAD4 genome AF: 0.538 AC: 81849 AN: 152064 Hom.: 24176 Cov.: 33 AF XY: 0.540 AC XY: 40100 AN XY: 74324

African (AFR) AF: 0.742 AC: 30789 AN: 41502

American (AMR) AF: 0.577 AC: 8805 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.494 AC: 1713 AN: 3470

East Asian (EAS) AF: 0.767 AC: 3975 AN: 5184

South Asian (SAS) AF: 0.739 AC: 3562 AN: 4818

European-Finnish (FIN) AF: 0.296 AC: 3124 AN: 10552

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.415 AC: 28185 AN: 67960

Other (OTH) AF: 0.533 AC: 1125 AN: 2112

Alfa AF: 0.467 Hom.: 32541

Bravo AF: 0.568

Asia WGS AF: 0.723 AC: 2512 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.0
DANN	Benign	0.82
PhyloP100		0.82
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11126426; hg19: chr2-74392940;