2-196656713-G-T

Variant names:

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

Variant summary

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

The NM_001080539.2(CCDC150):​c.257G>T​(p.Cys86Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,508 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/24 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C86Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: CCDC150 NM_001080539.2 missense
• Clinical Significance: Not reported in ClinVar
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC150	NM_001080539.2	c.257G>T	p.Cys86Phe	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>T	p.Cys86Phe	missense_variant	Exon 3 of 28	5	NM_001080539.2	ENSP00000373827.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000804 AC: 2 AN: 248720 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000888

Gnomad OTH exome AF: 0.000166

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461508 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727034

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53388

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111774

Other (OTH) AF: 0.0000166 AC: 1 AN: 60362

GnomAD4 genome Cov.: 32

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000122 AC: 1

ExAC AF: 0.0000166 AC: 2

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	16
DANN	Benign	0.65
DEOGEN2	Benign	0.0016	T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.47	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.089	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
PhyloP100		1.7
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.057
Sift	Benign	0.40	T
Sift4G	Benign	1.0	T
Polyphen		0.0010	B
Vest4		0.28
MVP		0.12
MPC		0.054
ClinPred		0.038	T
GERP RS		4.1
Varity_R		0.13
gMVP		0.057
Mutation Taster		=279/21	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.28		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.28		Position offset: 6

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs370426343; hg19: chr2-197521437;