rs2277026

Positions:

• chr5-157317172-G-A
• chr5-157317172-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.81

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYFIP2	NM_001037333.3	c.1356+2078G>A		intron_variant		ENST00000620254.5	NP_001032410.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYFIP2	ENST00000620254.5	c.1356+2078G>A		intron_variant		1	NM_001037333.3	ENSP00000479968	P1

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48675 AN: 151588 Hom.: 8608 Cov.: 32

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.: 32 AF XY: 0.321 AC XY: 23773 AN XY: 74098

Gnomad4 AFR AF: 0.478

Gnomad4 AMR AF: 0.197

Gnomad4 ASJ AF: 0.337

Gnomad4 EAS AF: 0.265

Gnomad4 SAS AF: 0.294

Gnomad4 FIN AF: 0.317

Gnomad4 NFE AF: 0.263

Gnomad4 OTH AF: 0.295

Alfa AF: 0.256 Hom.: 2397

Bravo AF: 0.320

Asia WGS AF: 0.261 AC: 908 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.089
DANN	Benign	0.64

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

Other links and lift over

dbSNP: rs2277026; hg19: chr5-156744180; COSMIC: COSV59031544; COSMIC: COSV59031544;