10-32451722-A-G

Position:

• chr10-32451722-A-G

Variant summary

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

The NM_001395015.1(CCDC7):​c.80A>G​(p.His27Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,824 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 32)
  • Exomes 𝑓: 0.0000082 (0 hom.)
• Consequence: CCDC7 NM_001395015.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.561

Genes affected

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

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=0.043848127).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC7	NM_001395015.1	c.80A>G	p.His27Arg	missense_variant	2/44	ENST00000639629.2	NP_001381944.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC7	ENST00000639629.2	c.80A>G	p.His27Arg	missense_variant	2/44	5	NM_001395015.1	ENSP00000491655	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000821 AC: 12 AN: 1461824 Hom.: 0 Cov.: 30 AF XY: 0.00000688 AC XY: 5 AN XY: 727208

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000989

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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 16, 2024

The c.80A>G (p.H27R) alteration is located in exon 2 (coding exon 1) of the CCDC7 gene. This alteration results from a A to G substitution at nucleotide position 80, causing the histidine (H) at amino acid position 27 to be replaced by an arginine (R). 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	0.072
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.13
DANN	Benign	0.15
DEOGEN2	Benign	0.0059	.;.;T;T;T;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.59	.;T;T;T;T;T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.044	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.69	N;N;.;.;.;N
MutationTaster	Benign	1.0	N;N;N;N;N;N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.21	N;N;N;N;N;.
REVEL	Benign	0.035
Sift	Benign	0.43	T;T;T;T;T;.
Sift4G	Benign	0.48	T;T;T;T;T;.
Polyphen		0.0	.;.;B;.;.;B
Vest4		0.16
MutPred		0.20		Gain of MoRF binding (P = 0.0165);Gain of MoRF binding (P = 0.0165);Gain of MoRF binding (P = 0.0165);Gain of MoRF binding (P = 0.0165);Gain of MoRF binding (P = 0.0165);Gain of MoRF binding (P = 0.0165);
MVP		0.17
MPC		0.069
ClinPred		0.026	T
GERP RS		-2.4
Varity_R		0.029
gMVP		0.0090

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: rs2033121627; hg19: chr10-32740650;