chr2-130139670-A-G

Variant names:

• chr2-130139670-A-G
• NM_001258307.2:c.830T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001258307.2(CCDC74B):​c.830T>C​(p.Val277Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CCDC74B NM_001258307.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.402
• Publications: 0 publications found

Genes affected

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

MED15P9 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04216218).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001258307.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC74B	NM_001258307.2	MANE Select	c.830T>C	p.Val277Ala	missense	Exon 8 of 8	NP_001245236.1	Q96LY2-2
	CCDC74B	NM_207310.4		c.1028T>C	p.Val343Ala	missense	Exon 8 of 8	NP_997193.1	Q96LY2-1
	CCDC74B	NR_165309.1		n.1113T>C		non_coding_transcript_exon	Exon 8 of 8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC74B	ENST00000409943.8	TSL:1 MANE Select	c.830T>C	p.Val277Ala	missense	Exon 8 of 8	ENSP00000386294.3	Q96LY2-2
	CCDC74B	ENST00000860854.1		c.1040T>C	p.Val347Ala	missense	Exon 8 of 8	ENSP00000530913.1
	CCDC74B	ENST00000944366.1		c.1040T>C	p.Val347Ala	missense	Exon 8 of 8	ENSP00000614425.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460818 Hom.: 0 Cov.: 42 AF XY: 0.00 AC XY: 0 AN XY: 726726

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.0000224 AC: 1 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52788

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5504

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111950

Other (OTH) AF: 0.00 AC: 0 AN: 60344

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	0.34
DANN	Benign	0.33
DEOGEN2	Benign	0.0011	T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.033	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.042	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.77	N
PhyloP100		-0.40
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.60	N
REVEL	Benign	0.032
Sift	Benign	0.55	T
Sift4G	Benign	1.0	T
Polyphen		0.0010	B
Vest4		0.022
MVP		0.47
MPC		0.17
ClinPred		0.036	T
GERP RS		-2.0
Varity_R		0.028
gMVP		0.032
Mutation Taster		=99/1	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

hg19: chr2-130897243;