chr2-56192781-G-A

Position:

• chr2-56192781-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001080433.2(CCDC85A):​c.581G>A​(p.Cys194Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,460,982 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CCDC85A NM_001080433.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.40

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.42026716).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC85A	NM_001080433.2	c.581G>A	p.Cys194Tyr	missense_variant	2/6	ENST00000407595.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC85A	ENST00000407595.3	c.581G>A	p.Cys194Tyr	missense_variant	2/6	1	NM_001080433.2	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000404 AC: 1 AN: 247256 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 134396

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000557

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1460982 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726706

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000825 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 22, 2024

The c.581G>A (p.C194Y) alteration is located in exon 2 (coding exon 2) of the CCDC85A gene. This alteration results from a G to A substitution at nucleotide position 581, causing the cysteine (C) at amino acid position 194 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Benign	-0.084	T
BayesDel_noAF	Benign	-0.19
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.031	T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.42	T
MetaSVM	Benign	-0.51	T
MutationAssessor	Benign	1.5	L
MutationTaster	Benign	0.93	D;D
PrimateAI	Uncertain	0.77	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.24
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.020	D
Polyphen		1.0	D
Vest4		0.56
MutPred		0.44		Gain of phosphorylation at C194 (P = 0.0555);
MVP		0.43
MPC		0.56
ClinPred		0.81	D
GERP RS		5.2
Varity_R		0.47
gMVP		0.15

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: rs747966842; hg19: chr2-56419916;