10-32451884-A-G

Variant names:

• chr10-32451884-A-G
• NM_001395015.1:c.242A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001395015.1(CCDC7):​c.242A>G​(p.Asp81Gly) 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. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D81H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCDC7 NM_001395015.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.49
• Publications: 0 publications found

Genes affected

CCDC7 (HGNC:26533): (coiled-coil domain containing 7)

CCDC7 Gene-Disease associations (from GenCC):

• Tourette syndrome

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2637878).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395015.1. 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
	CCDC7	NM_001395015.1	MANE Select	c.242A>G	p.Asp81Gly	missense	Exon 2 of 44	NP_001381944.1	Q96M83-1
	CCDC7	NM_001321115.2		c.242A>G	p.Asp81Gly	missense	Exon 2 of 44	NP_001308044.1	Q96M83-1
	CCDC7	NM_001395233.1		c.242A>G	p.Asp81Gly	missense	Exon 2 of 15	NP_001382162.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC7	ENST00000639629.2	TSL:5 MANE Select	c.242A>G	p.Asp81Gly	missense	Exon 2 of 44	ENSP00000491655.1	Q96M83-1
	CCDC7	ENST00000277657.12	TSL:1	c.242A>G	p.Asp81Gly	missense	Exon 2 of 18	ENSP00000277657.6	Q96M83-3
	CCDC7	ENST00000362006.11	TSL:1	c.242A>G	p.Asp81Gly	missense	Exon 2 of 18	ENSP00000355078.5	Q96M83-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	0.17
BayesDel_addAF	Benign	-0.070	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.067	T
Eigen	Uncertain	0.19
Eigen_PC	Benign	0.19
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	1.9	L
PhyloP100		1.5
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.22
Sift	Benign	0.13	T
Sift4G	Benign	0.28	T
Polyphen		0.93	P
Vest4		0.57
MutPred		0.29		Loss of helix (P = 0.0167)
MVP		0.54
MPC		0.091
ClinPred		0.71	D
GERP RS		5.4
PromoterAI		-0.076	Neutral
Varity_R		0.17
gMVP		0.056
Mutation Taster		=88/12	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

hg19: chr10-32740812;