2-130142157-A-T

Position:

• chr2-130142157-A-T

Variant summary

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

The NM_001258307.2(CCDC74B):​c.322T>A​(p.Ser108Thr) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: CCDC74B NM_001258307.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.81

Genes affected

CCDC74B (HGNC:25267): (coiled-coil domain containing 74B)

CCDC74B (HGNC:):

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=0.16024286).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC74B	NM_001258307.2	c.322T>A	p.Ser108Thr	missense_variant	3/8	ENST00000409943.8	NP_001245236.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC74B	ENST00000409943.8	c.322T>A	p.Ser108Thr	missense_variant	3/8	1	NM_001258307.2	ENSP00000386294.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 31

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

Oct 04, 2022

The c.520T>A (p.S174T) alteration is located in exon 3 (coding exon 3) of the CCDC74B gene. This alteration results from a T to A substitution at nucleotide position 520, causing the serine (S) at amino acid position 174 to be replaced by a threonine (T). 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	0.11
BayesDel_addAF	Benign	-0.081	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	12
DANN	Benign	0.84
DEOGEN2	Benign	0.016	.;T;.;.
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.53	T;T;T;T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.16	T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.4	.;L;.;.
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-2.1	N;N;.;N
REVEL	Benign	0.070
Sift	Benign	0.15	T;D;.;D
Sift4G	Benign	0.58	T;T;D;T
Polyphen		0.59	P;P;.;.
Vest4		0.23
MVP		0.71
MPC		2.5
ClinPred		0.19	T
GERP RS		2.2
Varity_R		0.14
gMVP		0.15

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: chr2-130899730;