2-196656713-G-A

Variant names:

• chr2-196656713-G-A
• rs370426343
• NM_001080539.2:c.257G>A

Variant summary

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

The NM_001080539.2(CCDC150):​c.257G>A​(p.Cys86Tyr) 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. 15/22 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)
• Consequence: CCDC150 NM_001080539.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.69
• Publications: 1 publications found

Genes affected

CCDC150 (HGNC:26834): (coiled-coil domain containing 150)

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=0.12289375).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC150	NM_001080539.2	c.257G>A	p.Cys86Tyr	missense_variant	Exon 3 of 28	ENST00000389175.9	NP_001074008.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC150	ENST00000389175.9	c.257G>A	p.Cys86Tyr	missense_variant	Exon 3 of 28	5	NM_001080539.2	ENSP00000373827.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 16, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.257G>A (p.C86Y) alteration is located in exon 3 (coding exon 3) of the CCDC150 gene. This alteration results from a G to A substitution at nucleotide position 257, causing the cysteine (C) at amino acid position 86 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	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	15
DANN	Benign	0.28
DEOGEN2	Benign	0.0062	T
Eigen	Benign	-0.098
Eigen_PC	Benign	-0.012
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M
PhyloP100		1.7
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.12
Sift	Benign	0.32	T
Sift4G	Benign	0.54	T
Polyphen		0.22	B
Vest4		0.27
MutPred		0.52		Gain of catalytic residue at C86 (P = 0.018);
MVP		0.14
MPC		0.046
ClinPred		0.21	T
GERP RS		4.1
Varity_R		0.082
gMVP		0.062
Mutation Taster		=279/21	polymorphism

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

Other links and lift over

dbSNP: rs370426343; hg19: chr2-197521437;