Variant chr5-157285374-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 3P and 6B. PM2PP2BP6_ModerateBS2

The NM_001037333.3(CYFIP2):c.13G>A(p.Val5Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000353 in 1,418,230 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

CYFIP2
NM_001037333.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 9.75

Variant links:

Genes affected

CYFIP2 (HGNC:13760): (cytoplasmic FMR1 interacting protein 2) Predicted to enable small GTPase binding activity. Involved in activation of cysteine-type endopeptidase activity; apoptotic process; and cell-cell adhesion. Located in perinuclear region of cytoplasm and synapse. Part of SCAR complex. Implicated in developmental and epileptic encephalopathy 65. [provided by Alliance of Genome Resources, Apr 2022]

CYFIP2 links:

CYFIP2 (HGNC:):

CYFIP2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), CYFIP2. . Gene score misZ 6.0129 (greater than the threshold 3.09). Trascript score misZ 6.9267 (greater than threshold 3.09). GenCC has associacion of gene with developmental and epileptic encephalopathy, 65, developmental and epileptic encephalopathy, 76, undetermined early-onset epileptic encephalopathy.

BP6

Variant 5-157285374-G-A is Benign according to our data. Variant chr5-157285374-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2110786.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYFIP2	NM_001037333.3 linkuse as main transcript	c.13G>A	p.Val5Ile	missense_variant	2/31	ENST00000620254.5	NP_001032410.1	Q96F07-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYFIP2	ENST00000620254.5 linkuse as main transcript	c.13G>A	p.Val5Ile	missense_variant	2/31	1	NM_001037333.3	ENSP00000479968.1		Q96F07-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000353

AC:

AN:

1418230

Hom.:

Cov.:

AF XY:

0.00000570

AC XY:

AN XY:

701146

show subpopulations

Gnomad4 AFR exome

AF:

0.0000308

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000396

Gnomad4 NFE exome

AF:

0.00000184

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 10, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.062

BayesDel_noAF

Benign

-0.33

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

T;.;.;T;T;T;.;.;.

Eigen

Uncertain

0.63

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.91

D;.;D;D;D;D;D;D;D

M_CAP

Benign

0.0080

MetaRNN

Uncertain

0.47

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.8

L;L;.;.;.;.;.;.;L

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-0.50

.;.;N;.;N;.;.;.;.

REVEL

Benign

0.17

Sift

Benign

0.14

.;.;T;.;T;.;.;.;.

Sift4G

Benign

0.11

T;T;T;T;T;T;T;T;T

Polyphen

0.86

P;P;P;.;D;.;.;.;P

Vest4

0.49

MutPred

0.47

Gain of loop (P = 0.2045);Gain of loop (P = 0.2045);Gain of loop (P = 0.2045);Gain of loop (P = 0.2045);Gain of loop (P = 0.2045);Gain of loop (P = 0.2045);Gain of loop (P = 0.2045);Gain of loop (P = 0.2045);Gain of loop (P = 0.2045);

MVP

0.34

MPC

1.1

ClinPred

0.74

GERP RS

5.6

Varity_R

0.24

gMVP

0.91

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

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