NM_001162499.2:c.992A>T

Variant names:

• chr3-12813374-A-T
• rs138783925
• NM_001162499.2:c.992A>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.992A>T​(p.Glu331Val) variant causes a missense change. The variant allele was found at a frequency of 0.00601 in 1,613,728 control chromosomes in the GnomAD database, including 41 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0053 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0061 (40 hom.)
• Consequence: CAND2 NM_001162499.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.31
• Publications: 13 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=0.0043477714).
• BP6: Variant 3-12813374-A-T is Benign according to our data. Variant chr3-12813374-A-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2653547.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 40 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.992A>T	p.Glu331Val	missense	Exon 7 of 15	NP_001155971.1	O75155-1
	CAND2	NM_012298.3		c.713A>T	p.Glu238Val	missense	Exon 5 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.992A>T	p.Glu331Val	missense	Exon 7 of 15	ENSP00000387641.2	O75155-1
	CAND2	ENST00000295989.9	TSL:1	c.713A>T	p.Glu238Val	missense	Exon 5 of 13	ENSP00000295989.5	O75155-2
	CAND2	ENST00000856238.1		c.713A>T	p.Glu238Val	missense	Exon 5 of 13	ENSP00000526297.1

Frequencies

GnomAD3 genomes AF: 0.00527 AC: 802 AN: 152190 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00140

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00772

Gnomad ASJ AF: 0.0147

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00310

Gnomad FIN AF: 0.00198

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00764

Gnomad OTH AF: 0.00813

GnomAD2 exomes AF: 0.00559 AC: 1390 AN: 248814 AF XY: 0.00581

Gnomad AFR exome AF: 0.00129

Gnomad AMR exome AF: 0.00595

Gnomad ASJ exome AF: 0.0132

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00293

Gnomad NFE exome AF: 0.00736

Gnomad OTH exome AF: 0.0106

GnomAD4 exome AF: 0.00609 AC: 8893 AN: 1461420 Hom.: 40 Cov.: 32 AF XY: 0.00607 AC XY: 4413 AN XY: 727002

African (AFR) AF: 0.00123 AC: 41 AN: 33468

American (AMR) AF: 0.00586 AC: 262 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.0145 AC: 378 AN: 26116

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

South Asian (SAS) AF: 0.00234 AC: 202 AN: 86192

European-Finnish (FIN) AF: 0.00318 AC: 170 AN: 53402

Middle Eastern (MID) AF: 0.0112 AC: 64 AN: 5690

European-Non Finnish (NFE) AF: 0.00660 AC: 7336 AN: 1111790

Other (OTH) AF: 0.00725 AC: 438 AN: 60376

GnomAD4 genome AF: 0.00527 AC: 803 AN: 152308 Hom.: 1 Cov.: 32 AF XY: 0.00482 AC XY: 359 AN XY: 74472

African (AFR) AF: 0.00140 AC: 58 AN: 41558

American (AMR) AF: 0.00771 AC: 118 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0147 AC: 51 AN: 3472

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

South Asian (SAS) AF: 0.00331 AC: 16 AN: 4828

European-Finnish (FIN) AF: 0.00198 AC: 21 AN: 10624

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00764 AC: 520 AN: 68020

Other (OTH) AF: 0.00804 AC: 17 AN: 2114

Alfa AF: 0.00744 Hom.: 4

Bravo AF: 0.00543

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.00829

EpiControl AF: 0.00818

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	0.19
PhyloP100		5.3
Varity_R		0.41
gMVP		0.43
Mutation Taster		=86/14	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs138783925; hg19: chr3-12854873;