chr2-56184662-C-T

Variant names:

• chr2-56184662-C-T
• rs573551108
• NM_001080433.2:c.38C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001080433.2(CCDC85A):​c.38C>T​(p.Ala13Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000962 in 1,455,798 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: CCDC85A NM_001080433.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.36
• Publications: 1 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.046206057).

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.38C>T	p.Ala13Val	missense	Exon 1 of 6	NP_001073902.1	Q96PX6
	CCDC85A	NM_001348512.1		c.38C>T	p.Ala13Val	missense	Exon 1 of 7	NP_001335441.1
	CCDC85A	NM_001348513.1		c.38C>T	p.Ala13Val	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.38C>T	p.Ala13Val	missense	Exon 1 of 6	ENSP00000384040.2	Q96PX6
	ENSG00000233251	ENST00000432793.6	TSL:1	n.100+1036G>A		intron	N/A
	CCDC85A	ENST00000894231.1		c.38C>T	p.Ala13Val	missense	Exon 1 of 7	ENSP00000564290.1

Frequencies

GnomAD3 genomes AF: 0.00000659 AC: 1 AN: 151860 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: 0.000194

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 55578 AF XY: 0.00

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000997 AC: 13 AN: 1303830 Hom.: 0 Cov.: 30 AF XY: 0.00000779 AC XY: 5 AN XY: 641538

African (AFR) AF: 0.00 AC: 0 AN: 24962

American (AMR) AF: 0.00 AC: 0 AN: 18496

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20672

East Asian (EAS) AF: 0.00 AC: 0 AN: 30084

South Asian (SAS) AF: 0.00 AC: 0 AN: 66314

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37132

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3748

European-Non Finnish (NFE) AF: 0.0000124 AC: 13 AN: 1048532

Other (OTH) AF: 0.00 AC: 0 AN: 53890

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151968 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74276

African (AFR) AF: 0.00 AC: 0 AN: 41476

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.000195 AC: 1 AN: 5128

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10576

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67910

Other (OTH) AF: 0.00 AC: 0 AN: 2106

Alfa AF: 0.000142 Hom.: 0

Bravo AF: 0.0000113

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	0.18
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0024	T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.054	D
MetaRNN	Benign	0.046	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.4
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-0.14	N
REVEL	Benign	0.045
Sift	Benign	1.0	T
Sift4G	Benign	0.25	T
Polyphen		0.0020	B
Vest4		0.26
MutPred		0.35		Gain of catalytic residue at A13 (P = 0.1066)
MVP		0.12
MPC		0.085
ClinPred		0.64	D
GERP RS		3.5
Varity_R		0.044
gMVP		0.35
Mutation Taster		=96/4	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: rs573551108; hg19: chr2-56411797; COSMIC: COSV105347386; COSMIC: COSV105347386;