chr2-117975255-G-A

Variant names:

• chr2-117975255-G-A
• rs17512204
• NM_019044.5:c.683C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_019044.5(CCDC93):​c.683C>T​(p.Pro228Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0717 in 1,612,948 control chromosomes in the GnomAD database, including 4,685 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.053 (286 hom., cov: 32)
  • Exomes 𝑓: 0.074 (4399 hom.)
• Consequence: CCDC93 NM_019044.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.65
• Publications: 24 publications found

Genes affected

CCDC93 (HGNC:25611): (coiled-coil domain containing 93) Involved in Golgi to plasma membrane transport and endocytic recycling. Located in intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017846525).
• BP6: Variant 2-117975255-G-A is Benign according to our data. Variant chr2-117975255-G-A is described in ClinVar as Benign. ClinVar VariationId is 1271261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0806 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019044.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC93	NM_019044.5	MANE Select	c.683C>T	p.Pro228Leu	missense	Exon 9 of 24	NP_061917.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC93	ENST00000376300.7	TSL:1 MANE Select	c.683C>T	p.Pro228Leu	missense	Exon 9 of 24	ENSP00000365477.2
	CCDC93	ENST00000884940.1		c.683C>T	p.Pro228Leu	missense	Exon 9 of 25	ENSP00000554999.1
	CCDC93	ENST00000951763.1		c.701C>T	p.Pro234Leu	missense	Exon 10 of 25	ENSP00000621822.1

Frequencies

GnomAD3 genomes AF: 0.0529 AC: 8050 AN: 152158 Hom.: 287 Cov.: 32

Gnomad AFR AF: 0.0129

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.0352

Gnomad ASJ AF: 0.0568

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0537

Gnomad FIN AF: 0.0697

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0824

Gnomad OTH AF: 0.0465

GnomAD2 exomes AF: 0.0564 AC: 14154 AN: 250852 AF XY: 0.0587

Gnomad AFR exome AF: 0.0118

Gnomad AMR exome AF: 0.0298

Gnomad ASJ exome AF: 0.0629

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.0710

Gnomad NFE exome AF: 0.0754

Gnomad OTH exome AF: 0.0656

GnomAD4 exome AF: 0.0736 AC: 107551 AN: 1460672 Hom.: 4399 Cov.: 31 AF XY: 0.0737 AC XY: 53592 AN XY: 726716

African (AFR) AF: 0.0116 AC: 387 AN: 33474

American (AMR) AF: 0.0307 AC: 1374 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.0608 AC: 1588 AN: 26132

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39700

South Asian (SAS) AF: 0.0611 AC: 5268 AN: 86252

European-Finnish (FIN) AF: 0.0740 AC: 3907 AN: 52798

Middle Eastern (MID) AF: 0.0702 AC: 404 AN: 5758

European-Non Finnish (NFE) AF: 0.0813 AC: 90333 AN: 1111468

Other (OTH) AF: 0.0710 AC: 4287 AN: 60380

GnomAD4 genome AF: 0.0528 AC: 8043 AN: 152276 Hom.: 286 Cov.: 32 AF XY: 0.0514 AC XY: 3829 AN XY: 74454

African (AFR) AF: 0.0128 AC: 534 AN: 41580

American (AMR) AF: 0.0351 AC: 537 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0568 AC: 197 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5178

South Asian (SAS) AF: 0.0535 AC: 258 AN: 4818

European-Finnish (FIN) AF: 0.0697 AC: 740 AN: 10610

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0824 AC: 5601 AN: 68008

Other (OTH) AF: 0.0460 AC: 97 AN: 2110

Alfa AF: 0.0700 Hom.: 1265

Bravo AF: 0.0481

TwinsUK AF: 0.0871 AC: 323

ALSPAC AF: 0.0771 AC: 297

ESP6500AA AF: 0.0138 AC: 61

ESP6500EA AF: 0.0809 AC: 696

ExAC AF: 0.0571 AC: 6936

Asia WGS AF: 0.0240 AC: 84 AN: 3478

EpiCase AF: 0.0809

EpiControl AF: 0.0759

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	20
DANN	Benign	0.65
DEOGEN2	Benign	0.0032	T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.41
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.88	D
MetaRNN	Benign	0.0018	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L
PhyloP100		4.6
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.89	N
REVEL	Benign	0.064
Sift	Benign	0.062	T
Sift4G	Benign	0.30	T
Polyphen		0.0070	B
Vest4		0.10
MPC		0.29
ClinPred		0.013	T
GERP RS		5.2
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.1
Varity_R		0.059
gMVP		0.27
Mutation Taster		=94/6	polymorphism (auto)

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

dbSNP: rs17512204; hg19: chr2-118732831;