Genetic Variant NM_001037333.3:c.111G>A (chr5-157285472-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001037333.3(CYFIP2):c.111G>A(p.Met37Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M37V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CYFIP2
NM_001037333.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.53

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
developmental and epileptic encephalopathy, 65
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Illumina, Labcorp Genetics (formerly Invitae)
undetermined early-onset epileptic encephalopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

CYFIP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.29276678).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001037333.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CYFIP2	NM_001037333.3	MANE Select	c.111G>A	p.Met37Ile	missense	Exon 2 of 31	NP_001032410.1	Q96F07-2
CYFIP2	NM_001291722.2		c.111G>A	p.Met37Ile	missense	Exon 2 of 32	NP_001278651.1	Q96F07-1
CYFIP2	NM_014376.4		c.111G>A	p.Met37Ile	missense	Exon 2 of 31	NP_055191.2	Q96F07-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CYFIP2	ENST00000620254.5	TSL:1 MANE Select	c.111G>A	p.Met37Ile	missense	Exon 2 of 31	ENSP00000479968.1	Q96F07-2
CYFIP2	ENST00000616178.4	TSL:1	c.111G>A	p.Met37Ile	missense	Exon 2 of 32	ENSP00000479719.1	Q96F07-1
CYFIP2	ENST00000618329.4	TSL:1	c.111G>A	p.Met37Ile	missense	Exon 2 of 31	ENSP00000484819.1	Q96F07-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1414158

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

698712

African (AFR)

AF:

0.00

AC:

AN:

32312

American (AMR)

AF:

0.00

AC:

AN:

37414

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25304

East Asian (EAS)

AF:

0.00

AC:

AN:

37098

South Asian (SAS)

AF:

0.00

AC:

AN:

80014

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50348

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5722

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1087180

Other (OTH)

AF:

0.00

AC:

AN:

58766

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.34

BayesDel_addAF

Benign

-0.015

BayesDel_noAF

Benign

-0.26

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.15

Eigen

Benign

-0.12

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.0080

MetaRNN

Benign

0.29

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-1.4

PhyloP100

6.5

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-0.62

REVEL

Benign

0.22

Sift

Benign

0.54

Sift4G

Benign

0.36

Polyphen

0.0040

Vest4

0.58

MutPred

0.43

Gain of sheet (P = 0.0827)

MVP

0.53

MPC

1.2

ClinPred

0.88

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.55

gMVP

0.91

Mutation Taster

=157/143

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over