3-12803514-C-T

Variant names:

• chr3-12803514-C-T
• rs62620196
• NM_001162499.2:c.95C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001162499.2(CAND2):​c.95C>T​(p.Ser32Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00733 in 1,612,434 control chromosomes in the GnomAD database, including 57 homozygotes. 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0049 (3 hom., cov: 31)
  • Exomes 𝑓: 0.0076 (54 hom.)
• Consequence: CAND2 NM_001162499.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.01
• Publications: 10 publications found

Genes affected

CAND2 (HGNC:30689): (cullin associated and neddylation dissociated 2 (putative)) Predicted to enable TBP-class protein binding activity. Predicted to be involved in SCF complex assembly; positive regulation of transcription, DNA-templated; and protein ubiquitination. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007929176).
• BP6: Variant 3-12803514-C-T is Benign according to our data. Variant chr3-12803514-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3387855.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001162499.2. 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
	CAND2	NM_001162499.2	MANE Select	c.95C>T	p.Ser32Leu	missense	Exon 2 of 15	NP_001155971.1	O75155-1
	CAND2	NM_012298.3		c.95C>T	p.Ser32Leu	missense	Exon 2 of 13	NP_036430.1	O75155-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAND2	ENST00000456430.6	TSL:1 MANE Select	c.95C>T	p.Ser32Leu	missense	Exon 2 of 15	ENSP00000387641.2	O75155-1
	CAND2	ENST00000295989.9	TSL:1	c.95C>T	p.Ser32Leu	missense	Exon 2 of 13	ENSP00000295989.5	O75155-2
	CAND2	ENST00000856238.1		c.95C>T	p.Ser32Leu	missense	Exon 2 of 13	ENSP00000526297.1

Frequencies

GnomAD3 genomes AF: 0.00489 AC: 744 AN: 152164 Hom.: 3 Cov.: 31

Gnomad AFR AF: 0.00162

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00294

Gnomad ASJ AF: 0.00922

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.000565

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00841

Gnomad OTH AF: 0.00574

GnomAD2 exomes AF: 0.00557 AC: 1379 AN: 247530 AF XY: 0.00567

Gnomad AFR exome AF: 0.00154

Gnomad AMR exome AF: 0.00367

Gnomad ASJ exome AF: 0.00965

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00163

Gnomad NFE exome AF: 0.00855

Gnomad OTH exome AF: 0.00699

GnomAD4 exome AF: 0.00759 AC: 11085 AN: 1460152 Hom.: 54 Cov.: 30 AF XY: 0.00765 AC XY: 5553 AN XY: 726314

African (AFR) AF: 0.00138 AC: 46 AN: 33440

American (AMR) AF: 0.00348 AC: 155 AN: 44576

Ashkenazi Jewish (ASJ) AF: 0.00937 AC: 244 AN: 26052

East Asian (EAS) AF: 0.0000505 AC: 2 AN: 39632

South Asian (SAS) AF: 0.00305 AC: 262 AN: 86032

European-Finnish (FIN) AF: 0.00154 AC: 82 AN: 53226

Middle Eastern (MID) AF: 0.00503 AC: 29 AN: 5760

European-Non Finnish (NFE) AF: 0.00886 AC: 9842 AN: 1111124

Other (OTH) AF: 0.00701 AC: 423 AN: 60310

GnomAD4 genome AF: 0.00487 AC: 742 AN: 152282 Hom.: 3 Cov.: 31 AF XY: 0.00459 AC XY: 342 AN XY: 74468

African (AFR) AF: 0.00161 AC: 67 AN: 41556

American (AMR) AF: 0.00294 AC: 45 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00922 AC: 32 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4824

European-Finnish (FIN) AF: 0.000565 AC: 6 AN: 10612

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00841 AC: 572 AN: 68016

Other (OTH) AF: 0.00568 AC: 12 AN: 2112

Alfa AF: 0.00801 Hom.: 15

Bravo AF: 0.00502

TwinsUK AF: 0.00620 AC: 23

ALSPAC AF: 0.00778 AC: 30

ESP6500AA AF: 0.00114 AC: 5

ESP6500EA AF: 0.00826 AC: 71

ExAC AF: 0.00557 AC: 676

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.00961

EpiControl AF: 0.0104

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.021	T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.20	N
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.0079	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.52	N
PhyloP100		1.0
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.026
Sift	Benign	0.27	T
Sift4G	Benign	0.36	T
Polyphen		0.0010	B
Vest4		0.16
MVP		0.71
MPC		1.0
ClinPred		0.0051	T
GERP RS		2.8
Varity_R		0.042
gMVP		0.13
Mutation Taster		=94/6	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: rs62620196; hg19: chr3-12845013; COSMIC: COSV55994049; COSMIC: COSV55994049;