chr2-168871505-C-G

Variant names:

• chr2-168871505-C-G
• rs767881744
• NM_020675.4:c.601G>C

Variant summary

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

The NM_020675.4(SPC25):​c.601G>C​(p.Val201Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,457,490 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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. V201I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SPC25 NM_020675.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00400
• Publications: 0 publications found

Genes affected

SPC25 (HGNC:24031): (SPC25 component of NDC80 kinetochore complex) This gene encodes a protein that may be involved in kinetochore-microtubule interaction and spindle checkpoint activity. [provided by RefSeq, Jul 2008]

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=0.045668393).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020675.4. 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
	SPC25	NM_020675.4	MANE Select	c.601G>C	p.Val201Leu	missense	Exon 7 of 7	NP_065726.1	Q9HBM1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPC25	ENST00000282074.7	TSL:1 MANE Select	c.601G>C	p.Val201Leu	missense	Exon 7 of 7	ENSP00000282074.2	Q9HBM1
	SPC25	ENST00000861849.1		c.601G>C	p.Val201Leu	missense	Exon 8 of 8	ENSP00000531908.1
	SPC25	ENST00000861850.1		c.601G>C	p.Val201Leu	missense	Exon 7 of 7	ENSP00000531909.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1457490 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 724724

African (AFR) AF: 0.00 AC: 0 AN: 33240

American (AMR) AF: 0.0000452 AC: 2 AN: 44232

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26024

East Asian (EAS) AF: 0.00 AC: 0 AN: 39526

South Asian (SAS) AF: 0.00 AC: 0 AN: 84986

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53304

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110238

Other (OTH) AF: 0.00 AC: 0 AN: 60196

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	12
DANN	Benign	0.84
DEOGEN2	Benign	0.042	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.051	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.046	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.14	N
PhyloP100		-0.0040
PrimateAI	Benign	0.47	T
PROVEAN	Benign	0.48	N
REVEL	Benign	0.032
Sift	Benign	0.69	T
Sift4G	Benign	0.79	T
Polyphen		0.0010	B
Vest4		0.22
MutPred		0.51		Loss of MoRF binding (P = 0.104)
MVP		0.13
MPC		0.22
ClinPred		0.058	T
GERP RS		0.60
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.15
gMVP		0.34
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs767881744; hg19: chr2-169728015;