rs2272239

Variant names:

• chr2-74178740-T-C
• rs2272239
• NM_018221.5:c.-66A>G

Your query was ambiguous. Multiple possible variants found:

• chr2-74178740-T-C
• chr2-74178740-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018221.5(MOB1A):​c.-66A>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000128 in 779,030 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000013 (0 hom.)
• Consequence: MOB1A NM_018221.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0860
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018221.5. 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
	MOB1A	NM_018221.5	MANE Select	c.-66A>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 6	NP_060691.2	Q9H8S9-1
	MOB1A	NM_018221.5	MANE Select	c.-66A>G		5_prime_UTR	Exon 1 of 6	NP_060691.2	Q9H8S9-1
	MOB1A	NM_001317110.2		c.-66A>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 6	NP_001304039.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MOB1A	ENST00000396049.5	TSL:1 MANE Select	c.-66A>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 6	ENSP00000379364.3	Q9H8S9-1
	MOB1A	ENST00000396049.5	TSL:1 MANE Select	c.-66A>G		5_prime_UTR	Exon 1 of 6	ENSP00000379364.3	Q9H8S9-1
	MOB1A	ENST00000882072.1		c.-66A>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 6	ENSP00000552131.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000128 AC: 1 AN: 779030 Hom.: 0 Cov.: 10 AF XY: 0.00 AC XY: 0 AN XY: 377772

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 16568

American (AMR) AF: 0.00 AC: 0 AN: 7638

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12154

East Asian (EAS) AF: 0.00 AC: 0 AN: 24372

South Asian (SAS) AF: 0.00 AC: 0 AN: 19994

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32260

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3142

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 629950

Other (OTH) AF: 0.0000303 AC: 1 AN: 32952

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	11
DANN	Benign	0.76
PhyloP100		0.086
PromoterAI		-0.022	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2272239;

hg19: chr2-74405867;