chr5-157285487-A-C

Variant names:

• chr5-157285487-A-C
• NM_001037333.3:c.117+9A>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001037333.3(CYFIP2):​c.117+9A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CYFIP2 NM_001037333.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0580
• Publications: 0 publications found

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

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 5-157285487-A-C is Benign according to our data. Variant chr5-157285487-A-C is described in ClinVar as Benign. ClinVar VariationId is 2028387.Status of the report is criteria_provided_single_submitter, 1 stars.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYFIP2	NM_001037333.3	MANE Select	c.117+9A>C		intron	N/A	NP_001032410.1	Q96F07-2
	CYFIP2	NM_001291722.2		c.117+9A>C		intron	N/A	NP_001278651.1	Q96F07-1
	CYFIP2	NM_014376.4		c.117+9A>C		intron	N/A	NP_055191.2	Q96F07-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYFIP2	ENST00000620254.5	TSL:1 MANE Select	c.117+9A>C		intron	N/A	ENSP00000479968.1	Q96F07-2
	CYFIP2	ENST00000616178.4	TSL:1	c.117+9A>C		intron	N/A	ENSP00000479719.1	Q96F07-1
	CYFIP2	ENST00000618329.4	TSL:1	c.117+9A>C		intron	N/A	ENSP00000484819.1	Q96F07-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	11
DANN	Benign	0.58
PhyloP100		-0.058

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

Other links and lift over

hg19: chr5-156712497;