11-65321177-G-C

Position:

• chr11-65321177-G-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_006779.4(CDC42EP2):​c.279G>C​(p.Gly93Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00164 in 1,614,066 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0086 (16 hom., cov: 32)
  • Exomes 𝑓: 0.00092 (19 hom.)
• Consequence: CDC42EP2 NM_006779.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0220

Genes affected

CDC42EP2 (HGNC:16263): (CDC42 effector protein 2) CDC42, a small Rho GTPase, regulates the formation of F-actin-containing structures through its interaction with the downstream effector proteins. The protein encoded by this gene is a member of the Borg family of CDC42 effector proteins. Borg family proteins contain a CRIB (Cdc42/Rac interactive-binding) domain. They bind to, and negatively regulate the function of CDC42. Coexpression of this protein with CDC42 suggested a role of this protein in actin filament assembly and cell shape control. [provided by RefSeq, Aug 2011]

ENSG00000285816 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 11-65321177-G-C is Benign according to our data. Variant chr11-65321177-G-C is described in ClinVar as [Benign]. Clinvar id is 785356.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.022 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00856 (1303/152252) while in subpopulation AFR AF= 0.03 (1246/41548). AF 95% confidence interval is 0.0286. There are 16 homozygotes in gnomad4. There are 604 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDC42EP2	NM_006779.4	c.279G>C	p.Gly93Gly	synonymous_variant	2/2	ENST00000279249.3	NP_006770.1
CDC42EP2	XM_047426244.1	c.279G>C	p.Gly93Gly	synonymous_variant	2/2		XP_047282200.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDC42EP2	ENST00000279249.3	c.279G>C	p.Gly93Gly	synonymous_variant	2/2	1	NM_006779.4	ENSP00000279249.2
ENSG00000285816	ENST00000649896.1	n.*605G>C		non_coding_transcript_exon_variant	19/20			ENSP00000498025.1
ENSG00000285816	ENST00000649896.1	n.*605G>C		3_prime_UTR_variant	19/20			ENSP00000498025.1
CDC42EP2	ENST00000533419.1	c.279G>C	p.Gly93Gly	synonymous_variant	2/2	3		ENSP00000431660.1

Frequencies

GnomAD3 genomes AF: 0.00855 AC: 1300 AN: 152134 Hom.: 16 Cov.: 32

Gnomad AFR AF: 0.0300

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00235

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00622

GnomAD3 exomes AF: 0.00217 AC: 544 AN: 251164 Hom.: 10 AF XY: 0.00152 AC XY: 207 AN XY: 135786

Gnomad AFR exome AF: 0.0307

Gnomad AMR exome AF: 0.000810

Gnomad ASJ exome AF: 0.0000994

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.000923 AC: 1349 AN: 1461814 Hom.: 19 Cov.: 32 AF XY: 0.000784 AC XY: 570 AN XY: 727198

Gnomad4 AFR exome AF: 0.0342

Gnomad4 AMR exome AF: 0.000962

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000696

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000180

Gnomad4 OTH exome AF: 0.00200

GnomAD4 genome AF: 0.00856 AC: 1303 AN: 152252 Hom.: 16 Cov.: 32 AF XY: 0.00811 AC XY: 604 AN XY: 74444

Gnomad4 AFR AF: 0.0300

Gnomad4 AMR AF: 0.00235

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.00616

Alfa AF: 0.000917 Hom.: 1

Bravo AF: 0.00937

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 23, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.5
DANN	Benign	0.41

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: rs4149836; hg19: chr11-65088648;