Genetic Variant NM_017437.3:c.1091T>G (chr14-92143245-T-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_017437.3(CPSF2):c.1091T>G(p.Leu364*) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 32)

Consequence

CPSF2
NM_017437.3 stop_gained

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.85

Publications

1 publications found

Variant links:

Genes affected

CPSF2 (HGNC:2325): (cleavage and polyadenylation specific factor 2) Predicted to enable RNA binding activity. Involved in mRNA 3'-end processing by stem-loop binding activity and cleavage. Located in membrane. Part of mRNA cleavage and polyadenylation specificity factor complex. [provided by Alliance of Genome Resources, Apr 2022]

CPSF2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017437.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CPSF2	NM_017437.3	MANE Select	c.1091T>G	p.Leu364*	stop_gained	Exon 9 of 16	NP_059133.1	Q9P2I0
CPSF2	NM_001322272.2		c.1091T>G	p.Leu364*	stop_gained	Exon 9 of 16	NP_001309201.1	Q9P2I0
CPSF2	NM_001322270.2		c.1091T>G	p.Leu364*	stop_gained	Exon 9 of 15	NP_001309199.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CPSF2	ENST00000298875.9	TSL:1 MANE Select	c.1091T>G	p.Leu364*	stop_gained	Exon 9 of 16	ENSP00000298875.4	Q9P2I0
CPSF2	ENST00000908829.1		c.1091T>G	p.Leu364*	stop_gained	Exon 9 of 16	ENSP00000578888.1
CPSF2	ENST00000932645.1		c.1091T>G	p.Leu364*	stop_gained	Exon 10 of 17	ENSP00000602704.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000400

AC:

AN:

250064

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000883

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.62

BayesDel_noAF

Pathogenic

0.65

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

Eigen

Pathogenic

0.86

Eigen_PC

Pathogenic

0.73

FATHMM_MKL

Pathogenic

0.99

PhyloP100

7.9

Vest4

0.52

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=3/197

disease causing (fs/PTC)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over