rs2061634

Variant names:

• chr9-97343500-C-G
• rs2061634
• NM_020893.6:c.2435C>G

Your query was ambiguous. Multiple possible variants found:

• chr9-97343500-C-G
• chr9-97343500-C-T

Variant summary

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

The NM_020893.6(CCDC180):​c.2435C>G​(p.Ser812Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 1,612,734 control chromosomes in the GnomAD database, including 58,719 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.30 (7274 hom., cov: 32)
  • Exomes 𝑓: 0.26 (51445 hom.)
• Consequence: CCDC180 NM_020893.6 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.620
• Publications: 35 publications found

Genes affected

CCDC180 (HGNC:29303): (coiled-coil domain containing 180) The protein encoded by this gene contains a coiled-coil domain. Alternative splicing results in multiple transcript variants encoding different isoforms. A single nucleotide polymorphism (SNP) in this gene has been associated with increased susceptibility to Behcet's Disease (PMID: 19442274). [provided by RefSeq, Dec 2016]

SUGT1P4-STRA6LP-CCDC180 (HGNC:53835): (SUGT1P4-STRA6LP-CCDC180 readthrough) This locus represents a set of read-through transcripts spanning an upstream pseudogene (GeneID:100499484) extending into a downstream protein-coding locus (GeneID:100499483). All of the read-through transcripts are candidates for nonsense-mediated decay (NMD), so they are not thought to express a protein. [provided by RefSeq, Aug 2010]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.0012887716).
• BP6: Variant 9-97343500-C-G is Benign according to our data. Variant chr9-97343500-C-G is described in ClinVar as Benign. ClinVar VariationId is 1268803.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.41 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC180	NM_020893.6	c.2435C>G	p.Ser812Cys	missense_variant	Exon 19 of 37	ENST00000529487.3	NP_065944.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC180	ENST00000529487.3	c.2435C>G	p.Ser812Cys	missense_variant	Exon 19 of 37	1	NM_020893.6	ENSP00000434727.2

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44827 AN: 151876 Hom.: 7265 Cov.: 32

Gnomad AFR AF: 0.415

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.267

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.290

GnomAD2 exomes AF: 0.266 AC: 66801 AN: 251382 AF XY: 0.265

Gnomad AFR exome AF: 0.413

Gnomad AMR exome AF: 0.296

Gnomad ASJ exome AF: 0.324

Gnomad EAS exome AF: 0.185

Gnomad FIN exome AF: 0.145

Gnomad NFE exome AF: 0.263

Gnomad OTH exome AF: 0.265

GnomAD4 exome AF: 0.261 AC: 381048 AN: 1460740 Hom.: 51445 Cov.: 35 AF XY: 0.262 AC XY: 190058 AN XY: 726740

African (AFR) AF: 0.420 AC: 14035 AN: 33442

American (AMR) AF: 0.301 AC: 13460 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.322 AC: 8404 AN: 26122

East Asian (EAS) AF: 0.162 AC: 6444 AN: 39694

South Asian (SAS) AF: 0.278 AC: 23977 AN: 86232

European-Finnish (FIN) AF: 0.153 AC: 8149 AN: 53394

Middle Eastern (MID) AF: 0.346 AC: 1994 AN: 5766

European-Non Finnish (NFE) AF: 0.259 AC: 287768 AN: 1111002

Other (OTH) AF: 0.279 AC: 16817 AN: 60372

GnomAD4 genome AF: 0.295 AC: 44876 AN: 151994 Hom.: 7274 Cov.: 32 AF XY: 0.288 AC XY: 21388 AN XY: 74308

African (AFR) AF: 0.415 AC: 17184 AN: 41414

American (AMR) AF: 0.294 AC: 4490 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.329 AC: 1142 AN: 3468

East Asian (EAS) AF: 0.183 AC: 948 AN: 5174

South Asian (SAS) AF: 0.267 AC: 1286 AN: 4808

European-Finnish (FIN) AF: 0.141 AC: 1495 AN: 10576

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.257 AC: 17445 AN: 67962

Other (OTH) AF: 0.289 AC: 610 AN: 2112

Alfa AF: 0.265 Hom.: 4203

Bravo AF: 0.312

TwinsUK AF: 0.257 AC: 952

ALSPAC AF: 0.255 AC: 982

ESP6500AA AF: 0.419 AC: 1846

ESP6500EA AF: 0.273 AC: 2349

ExAC AF: 0.269 AC: 32615

Asia WGS AF: 0.216 AC: 750 AN: 3478

EpiCase AF: 0.276

EpiControl AF: 0.271

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Feb 17, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 19442274) -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	14
DANN	Benign	0.96
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.040	N
LIST_S2	Benign	0.33	T
MetaRNN	Benign	0.0013	T
MetaSVM	Benign	-0.91	T
PhyloP100		0.62
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.038
Sift	Benign	0.088	T
Sift4G	Uncertain	0.0070	D
Vest4		0.099
ClinPred		0.0079	T
GERP RS		1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.067
gMVP		0.051
Mutation Taster		=93/7	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: rs2061634; hg19: chr9-100105782; COSMIC: COSV63830627;