16-66938169-C-G

Variant names:

• chr16-66938169-C-G
• rs752262052
• NM_001365405.1:c.209C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001365405.1(CES2):​c.209C>G​(p.Pro70Arg) 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. 15/19 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. P70L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CES2 NM_001365405.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.171
• Publications: 0 publications found

Genes affected

CES2 (HGNC:1864): (carboxylesterase 2) This gene encodes a member of the carboxylesterase large family. The family members are responsible for the hydrolysis or transesterification of various xenobiotics, such as cocaine and heroin, and endogenous substrates with ester, thioester, or amide bonds. They may participate in fatty acyl and cholesterol ester metabolism, and may play a role in the blood-brain barrier system. The protein encoded by this gene is the major intestinal enzyme and functions in intestine drug clearance. Alternatively spliced transcript variants have been found for this gene.[provided by RefSeq, Oct 2010]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15687558).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365405.1. 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
	CES2	NM_001365405.1	MANE Select	c.209C>G	p.Pro70Arg	missense	Exon 2 of 12	NP_001352334.1	O00748-1
	CES2	NM_003869.6		c.209C>G	p.Pro70Arg	missense	Exon 2 of 12	NP_003860.3
	CES2	NM_198061.3		c.209C>G	p.Pro70Arg	missense	Exon 2 of 12	NP_932327.2	O00748-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CES2	ENST00000317091.10	TSL:1 MANE Select	c.209C>G	p.Pro70Arg	missense	Exon 2 of 12	ENSP00000317842.5	O00748-1
	CES2	ENST00000417689.6	TSL:1	c.209C>G	p.Pro70Arg	missense	Exon 2 of 12	ENSP00000394452.2	O00748-2
	CES2	ENST00000971765.1		c.209C>G	p.Pro70Arg	missense	Exon 2 of 12	ENSP00000641824.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251460 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	0.47
DANN	Benign	0.93
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.060	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.77	T
PhyloP100		-0.17
PrimateAI	Benign	0.27	T
PROVEAN	Pathogenic	-5.3	D
REVEL	Benign	0.094
Sift	Benign	0.047	D
Sift4G	Uncertain	0.024	D
Vest4		0.17
MVP		0.12
MPC		0.21
ClinPred		0.40	T
GERP RS		-2.9

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: rs752262052; hg19: chr16-66972072;