rs760317264

Variant names:

• chr2-56184784-C-T
• rs760317264
• NM_001080433.2:c.160C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001080433.2(CCDC85A):​c.160C>T​(p.Arg54Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000647 in 1,546,384 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000065 (0 hom.)
• Consequence: CCDC85A NM_001080433.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.89
• Publications: 0 publications found

Genes affected

CCDC85A (HGNC:29400): (coiled-coil domain containing 85A) Located in adherens junction. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000233251 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080433.2. 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
	CCDC85A	NM_001080433.2	MANE Select	c.160C>T	p.Arg54Cys	missense	Exon 1 of 6	NP_001073902.1	Q96PX6
	CCDC85A	NM_001348512.1		c.160C>T	p.Arg54Cys	missense	Exon 1 of 7	NP_001335441.1
	CCDC85A	NM_001348513.1		c.160C>T	p.Arg54Cys	missense	Exon 1 of 6	NP_001335442.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC85A	ENST00000407595.3	TSL:1 MANE Select	c.160C>T	p.Arg54Cys	missense	Exon 1 of 6	ENSP00000384040.2	Q96PX6
	ENSG00000233251	ENST00000432793.6	TSL:1	n.100+914G>A		intron	N/A
	CCDC85A	ENST00000894231.1		c.160C>T	p.Arg54Cys	missense	Exon 1 of 7	ENSP00000564290.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152166 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000211 AC: 3 AN: 142496 AF XY: 0.0000130

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000392

Gnomad OTH exome AF: 0.000243

GnomAD4 exome AF: 0.00000646 AC: 9 AN: 1394218 Hom.: 0 Cov.: 35 AF XY: 0.00000436 AC XY: 3 AN XY: 687680

African (AFR) AF: 0.00 AC: 0 AN: 31090

American (AMR) AF: 0.00 AC: 0 AN: 35632

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25062

East Asian (EAS) AF: 0.00 AC: 0 AN: 35538

South Asian (SAS) AF: 0.00 AC: 0 AN: 78974

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47350

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4772

European-Non Finnish (NFE) AF: 0.00000835 AC: 9 AN: 1078026

Other (OTH) AF: 0.00 AC: 0 AN: 57774

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152166 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74318

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41460

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2092

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0000330 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000296 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	T
Eigen	Benign	0.16
Eigen_PC	Benign	0.050
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.054	D
MetaRNN	Uncertain	0.51	D
MetaSVM	Benign	-0.49	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		2.9
PrimateAI	Pathogenic	0.88	D
PROVEAN	Pathogenic	-5.2	D
REVEL	Uncertain	0.36
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.44
MutPred		0.69		Loss of MoRF binding (P = 0.0064)
MVP		0.33
MPC		0.53
ClinPred		0.98	D
GERP RS		3.4
Varity_R		0.60
gMVP		0.40
Mutation Taster		=84/16	polymorphism

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: rs760317264; hg19: chr2-56411919;