14-92143151-C-A

Variant names:

• chr14-92143151-C-A
• rs763407089
• NM_017437.3:c.997C>A

Variant summary

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

The NM_017437.3(CPSF2):​c.997C>A​(p.Leu333Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CPSF2 NM_017437.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.89
• Publications: 0 publications found

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]

ACMG classification

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPSF2	NM_017437.3	MANE Select	c.997C>A	p.Leu333Met	missense	Exon 9 of 16	NP_059133.1	Q9P2I0
	CPSF2	NM_001322272.2		c.997C>A	p.Leu333Met	missense	Exon 9 of 16	NP_001309201.1	Q9P2I0
	CPSF2	NM_001322270.2		c.997C>A	p.Leu333Met	missense	Exon 9 of 15	NP_001309199.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPSF2	ENST00000298875.9	TSL:1 MANE Select	c.997C>A	p.Leu333Met	missense	Exon 9 of 16	ENSP00000298875.4	Q9P2I0
	CPSF2	ENST00000908829.1		c.997C>A	p.Leu333Met	missense	Exon 9 of 16	ENSP00000578888.1
	CPSF2	ENST00000932645.1		c.997C>A	p.Leu333Met	missense	Exon 10 of 17	ENSP00000602704.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.062	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T
Eigen	Benign	0.17
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.55	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		1.9
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	0.050	N
REVEL	Benign	0.28
Sift	Benign	0.74	T
Sift4G	Benign	0.54	T
Polyphen		0.99	D
Vest4		0.66
MutPred		0.56		Gain of catalytic residue at L333 (P = 0.0045)
MVP		0.66
MPC		1.5
ClinPred		0.77	D
GERP RS		2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.16
gMVP		0.55
Mutation Taster		=57/43	polymorphism

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: rs763407089; hg19: chr14-92609495;