2-74474712-G-T

Position:

• chr2-74474712-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001365575.2(CCDC142):​c.2087C>A​(p.Ser696Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000226 in 1,461,890 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: 0.000023 (0 hom.)
• Consequence: CCDC142 NM_001365575.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.194

Genes affected

CCDC142 (HGNC:25889): (coiled-coil domain containing 142)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07719925).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC142	NM_001365575.2	c.2087C>A	p.Ser696Tyr	missense_variant	9/9	ENST00000393965.8
CCDC142	NM_032779.4	c.2066C>A	p.Ser689Tyr	missense_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC142	ENST00000393965.8	c.2087C>A	p.Ser696Tyr	missense_variant	9/9	1	NM_001365575.2	P2
CCDC142	ENST00000290418.4	c.2066C>A	p.Ser689Tyr	missense_variant	9/9	2		A2
CCDC142	ENST00000473278.1	n.657C>A		non_coding_transcript_exon_variant	3/3	2
CCDC142	ENST00000454193.5	c.1701+204C>A		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000226 AC: 33 AN: 1461890 Hom.: 0 Cov.: 32 AF XY: 0.0000248 AC XY: 18 AN XY: 727244

Gnomad4 AFR exome AF: 0.00

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: 0.0000297

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

Apr 26, 2023

The c.2066C>A (p.S689Y) alteration is located in exon 9 (coding exon 9) of the CCDC142 gene. This alteration results from a C to A substitution at nucleotide position 2066, causing the serine (S) at amino acid position 689 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	Benign	0.091
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	7.9
DANN	Benign	0.58
DEOGEN2	Benign	0.0070	T;.
Eigen	Benign	-0.93
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.065	N
LIST_S2	Benign	0.72	T;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.077	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-2.0	N;N
REVEL	Benign	0.021
Sift	Benign	0.089	T;T
Sift4G	Benign	0.32	T;T
Polyphen		0.081	B;B
Vest4		0.15
MutPred		0.19		Gain of catalytic residue at S696 (P = 0.0223);.;
MVP		0.17
MPC		0.42
ClinPred		0.053	T
GERP RS		2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.049
gMVP		0.24

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-74701839;