chr11-60842734-A-G

Position:

• chr11-60842734-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024098.4(CCDC86):​c.610A>G​(p.Thr204Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CCDC86 NM_024098.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.230

Genes affected

CCDC86 (HGNC:28359): (coiled-coil domain containing 86) Enables RNA binding activity. Located in chromosome; nucleolus; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

(HGNC:):

CCDC86-AS1 (HGNC:56314): (CCDC86 antisense RNA 1)

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.048613876).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC86	NM_024098.4	c.610A>G	p.Thr204Ala	missense_variant	1/4	ENST00000227520.10	NP_077003.1
CCDC86-AS1	NR_182293.1	n.317-754T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC86	ENST00000227520.10	c.610A>G	p.Thr204Ala	missense_variant	1/4	1	NM_024098.4	ENSP00000227520	P1
	ENST00000539897.1	n.232T>C		non_coding_transcript_exon_variant	1/2	4
CCDC86-AS1	ENST00000538705.1	n.317-754T>C		intron_variant, non_coding_transcript_variant		3
CCDC86	ENST00000535217.1	c.*29A>G		3_prime_UTR_variant, NMD_transcript_variant	2/5	5		ENSP00000442111

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

Bravo AF: 0.0000113

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

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

Aug 01, 2022

The c.610A>G (p.T204A) alteration is located in exon 1 (coding exon 1) of the CCDC86 gene. This alteration results from a A to G substitution at nucleotide position 610, causing the threonine (T) at amino acid position 204 to be replaced by an alanine (A). 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	Benign	0.089
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	4.9
DANN	Benign	0.75
DEOGEN2	Benign	0.075	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.069	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.049	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.057
Sift	Benign	0.22	T
Sift4G	Benign	0.26	T
Polyphen		0.035	B
Vest4		0.039
MVP		0.26
MPC		0.35
ClinPred		0.12	T
GERP RS		-1.5
Varity_R		0.032
gMVP		0.11

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: rs368729100; hg19: chr11-60610207;