Genetic Variant CYFIP2:c.1356+2078G>A (chr5-157317172-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001037333.3(CYFIP2):c.1356+2078G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 151,706 control chromosomes in the GnomAD database, including 8,633 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.32 ( 8633 hom., cov: 32)

Consequence

CYFIP2
NM_001037333.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.81

Publications

4 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.99).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

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	Effect	Exon Rank	Protein	UniProt
CYFIP2	NM_001037333.3	MANE Select	c.1356+2078G>A	intron	N/A	NP_001032410.1	Q96F07-2
CYFIP2	NM_001291722.2		c.1356+2078G>A	intron	N/A	NP_001278651.1	Q96F07-1
CYFIP2	NM_014376.4		c.1356+2078G>A	intron	N/A	NP_055191.2	Q96F07-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CYFIP2	ENST00000620254.5	TSL:1 MANE Select	c.1356+2078G>A	intron	N/A	ENSP00000479968.1	Q96F07-2
CYFIP2	ENST00000616178.4	TSL:1	c.1356+2078G>A	intron	N/A	ENSP00000479719.1	Q96F07-1
CYFIP2	ENST00000618329.4	TSL:1	c.1356+2078G>A	intron	N/A	ENSP00000484819.1	Q96F07-2

Frequencies

GnomAD3 genomes

AF:

0.321

AC:

48675

AN:

151588

Hom.:

8608

Cov.:

show subpopulations

Gnomad AFR

AF:

0.478

Gnomad AMI

AF:

0.164

Gnomad AMR

AF:

0.197

Gnomad ASJ

AF:

0.337

Gnomad EAS

AF:

0.265

Gnomad SAS

AF:

0.292

Gnomad FIN

AF:

0.317

Gnomad MID

AF:

0.297

Gnomad NFE

AF:

0.263

Gnomad OTH

AF:

0.297

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.321

AC:

48745

AN:

151706

Hom.:

8633

Cov.:

AF XY:

0.321

AC XY:

23773

AN XY:

74098

show subpopulations

African (AFR)

AF:

0.478

AC:

19792

AN:

41370

American (AMR)

AF:

0.197

AC:

2997

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.337

AC:

1170

AN:

3470

East Asian (EAS)

AF:

0.265

AC:

1367

AN:

5156

South Asian (SAS)

AF:

0.294

AC:

1403

AN:

4780

European-Finnish (FIN)

AF:

0.317

AC:

3322

AN:

10470

Middle Eastern (MID)

AF:

0.293

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.263

AC:

17840

AN:

67906

Other (OTH)

AF:

0.295

AC:

619

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1592

3183

4775

6366

7958

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

476

952

1428

1904

2380

<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:

0.261

Hom.:

2783

Bravo

AF:

0.320

Asia WGS

AF:

0.261

AC:

908

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

0.089

(source)

DANN

Benign

0.64

PhyloP100

-2.8

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over