NM_001325.3:c.787G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 1P and 8B. PP2BP4_StrongBS2

The NM_001325.3(CSTF2):c.787G>A(p.Ala263Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000053 in 1,208,584 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 17 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00025 ( 0 hom., 10 hem., cov: 22)

Exomes 𝑓: 0.000033 ( 0 hom. 7 hem. )

Consequence

CSTF2
NM_001325.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.00500

Publications

0 publications found

Variant links:

Genes affected

CSTF2 (HGNC:2484): (cleavage stimulation factor subunit 2) This gene encodes a nuclear protein with an RRM (RNA recognition motif) domain. The protein is a member of the cleavage stimulation factor (CSTF) complex that is involved in the 3' end cleavage and polyadenylation of pre-mRNAs. Specifically, this protein binds GU-rich elements within the 3'-untranslated region of mRNAs. [provided by RefSeq, Jul 2008]

CSTF2 Gene-Disease associations (from GenCC):

intellectual developmental disorder, X-linked 113
Inheritance: XL Classification: LIMITED Submitted by: Ambry Genetics

CSTF2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

PP2

Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 1 curated pathogenic missense variants (we use a threshold of 10). The gene has 0 curated benign missense variants. Gene score misZ: 3.4292 (above the threshold of 3.09). Trascript score misZ: NaN (below the threshold of 3.09). GenCC associations: The gene is linked to intellectual developmental disorder, X-linked 113.

BP4

Computational evidence support a benign effect (MetaRNN=0.014229089).

BS2

High Hemizygotes in GnomAd4 at 10 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001325.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CSTF2	NM_001325.3	MANE Select	c.787G>A	p.Ala263Thr	missense	Exon 7 of 14	NP_001316.1	P33240-1
CSTF2	NM_001306206.2		c.787G>A	p.Ala263Thr	missense	Exon 7 of 15	NP_001293135.1	E7EWR4
CSTF2	NM_001306209.2		c.736G>A	p.Ala246Thr	missense	Exon 7 of 14	NP_001293138.1	P33240-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CSTF2	ENST00000372972.7	TSL:1 MANE Select	c.787G>A	p.Ala263Thr	missense	Exon 7 of 14	ENSP00000362063.2	P33240-1
CSTF2	ENST00000415585.7	TSL:1	c.787G>A	p.Ala263Thr	missense	Exon 7 of 15	ENSP00000387996.2	E7EWR4
CSTF2	ENST00000866722.1		c.787G>A	p.Ala263Thr	missense	Exon 7 of 16	ENSP00000536781.1

Frequencies

GnomAD3 genomes

AF:

0.000251

AC:

AN:

111772

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000423

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00143

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000770

AC:

AN:

181899

AF XY:

0.0000753

show subpopulations

Gnomad AFR exome

AF:

0.000917

Gnomad AMR exome

AF:

0.0000367

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000222

GnomAD4 exome

AF:

0.0000328

AC:

AN:

1096760

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

362220

show subpopulations

African (AFR)

AF:

0.000758

AC:

AN:

26377

American (AMR)

AF:

0.000199

AC:

AN:

35151

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19367

East Asian (EAS)

AF:

0.00

AC:

AN:

30195

South Asian (SAS)

AF:

0.00

AC:

AN:

53979

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40485

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3973

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

841200

Other (OTH)

AF:

0.000196

AC:

AN:

46033

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000250

AC:

AN:

111824

Hom.:

Cov.:

AF XY:

0.000294

AC XY:

AN XY:

34026

show subpopulations

African (AFR)

AF:

0.000422

AC:

AN:

30813

American (AMR)

AF:

0.00142

AC:

AN:

10531

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2642

East Asian (EAS)

AF:

0.00

AC:

AN:

3566

South Asian (SAS)

AF:

0.00

AC:

AN:

2659

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6032

Middle Eastern (MID)

AF:

0.00

AC:

AN:

215

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53163

Other (OTH)

AF:

0.00

AC:

AN:

1525

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00129

Hom.:

Bravo

AF:

0.000419

ESP6500AA

AF:

0.000782

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000247

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.99

CADD

Benign

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.036

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.85

M_CAP

Benign

0.012

MetaRNN

Benign

0.014

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.2

PhyloP100

-0.0050

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.77

REVEL

Benign

0.034

Sift

Benign

0.081

Sift4G

Benign

0.52

Polyphen

0.0

Vest4

0.23

MVP

0.37

MPC

0.69

ClinPred

0.0043

GERP RS

-1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.058

gMVP

0.078

Mutation Taster

=98/2

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over