rs3207362

chr5-157309800-A-Gchr5-157309800-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_001037333.3(CYFIP2):c.958A>G(p.Lys320Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000000688 in 1,453,784 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CYFIP2 NM_001037333.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.34

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, CYFIP2
• BP4: Computational evidence support a benign effect (MetaRNN=0.22537285).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYFIP2	NM_001037333.3	c.958A>G	p.Lys320Glu	missense_variant	10/31	ENST00000620254.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYFIP2	ENST00000620254.5	c.958A>G	p.Lys320Glu	missense_variant	10/31	1	NM_001037333.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1453784 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 722098

Gnomad4 AFR exome AF: 0.00

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: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
Cadd	Uncertain	24
Dann	Uncertain	1.0
DEOGEN2	Uncertain	0.47	T;.;.;T;T;.
Eigen	Benign	0.14
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.72	T;.;T;T;T;T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.23	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M;M;.;.;.;M
MutationTaster	Benign	1.0	D;D;D;D;D;D;D
PrimateAI	Pathogenic	0.83	D
Sift4G	Benign	0.089	T;T;T;T;T;T
Polyphen		0.034	B;P;B;.;P;P
Vest4		0.25
MutPred		0.44		Loss of ubiquitination at K320 (P = 0.0326);Loss of ubiquitination at K320 (P = 0.0326);.;.;.;Loss of ubiquitination at K320 (P = 0.0326);
MVP		0.33
MPC		1.6
ClinPred		0.75	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.63
gMVP		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: rs3207362; hg19: chr5-156736808;