2-74474574-G-C

Position:

• chr2-74474574-G-C

Variant summary

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

The NM_001365575.2(CCDC142):​c.2225C>G​(p.Ser742Cys) 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. 12/21 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: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CCDC142 NM_001365575.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.707

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=0.23120803).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC142	NM_001365575.2	c.2225C>G	p.Ser742Cys	missense_variant	9/9	ENST00000393965.8
CCDC142	NM_032779.4	c.2204C>G	p.Ser735Cys	missense_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC142	ENST00000393965.8	c.2225C>G	p.Ser742Cys	missense_variant	9/9	1	NM_001365575.2	P2
CCDC142	ENST00000290418.4	c.2204C>G	p.Ser735Cys	missense_variant	9/9	2		A2
CCDC142	ENST00000473278.1	n.795C>G		non_coding_transcript_exon_variant	3/3	2
CCDC142	ENST00000454193.5	c.1701+342C>G		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1459364 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726046

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: 0.00

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

Nov 16, 2021

The c.2204C>G (p.S735C) alteration is located in exon 9 (coding exon 9) of the CCDC142 gene. This alteration results from a C to G substitution at nucleotide position 2204, causing the serine (S) at amino acid position 735 to be replaced by a cysteine (C). 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	0.078
BayesDel_addAF	Benign	-0.081	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.014	T;.
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.72	T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.3	M;.
MutationTaster	Benign	0.96	N;N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	0.45	N;N
REVEL	Benign	0.23
Sift	Uncertain	0.017	D;D
Sift4G	Benign	0.081	T;T
Polyphen		0.99	D;D
Vest4		0.31
MutPred		0.33		Loss of glycosylation at S742 (P = 0.0133);.;
MVP		0.65
MPC		0.74
ClinPred		0.69	D
GERP RS		1.9
Varity_R		0.050
gMVP		0.26

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr2-74701701;