Variant 9-104102152-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_006444.3(SMC2):c.829C>T(p.Leu277Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000771 in 1,577,210 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0041 ( 10 hom., cov: 32)

Exomes 𝑓: 0.00041 ( 6 hom. )

Consequence

SMC2
NM_006444.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.63

Variant links:

Genes affected

SMC2 (HGNC:14011): (structural maintenance of chromosomes 2) Predicted to enable ATP binding activity; chromatin binding activity; and single-stranded DNA binding activity. Involved in mitotic chromosome condensation. Located in condensed chromosome; cytoplasm; and nuclear lumen. Part of condensin complex. [provided by Alliance of Genome Resources, Apr 2022]

SMC2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0064918995).

BP6

Variant 9-104102152-C-T is Benign according to our data. Variant chr9-104102152-C-T is described in ClinVar as [Benign]. Clinvar id is 739502.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd at 629 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMC2	NM_006444.3 linkuse as main transcript	c.829C>T	p.Leu277Phe	missense_variant	8/25	ENST00000374793.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMC2	ENST00000374793.8 linkuse as main transcript	c.829C>T	p.Leu277Phe	missense_variant	8/25	1	NM_006444.3	P1	O95347-1
SMC2	ENST00000286398.11 linkuse as main transcript	c.829C>T	p.Leu277Phe	missense_variant	8/25	1		P1	O95347-1
SMC2	ENST00000374787.7 linkuse as main transcript	c.829C>T	p.Leu277Phe	missense_variant	8/25	2		P1	O95347-1
SMC2	ENST00000440179.5 linkuse as main transcript	c.394C>T	p.Leu132Phe	missense_variant	6/6	3

Frequencies

GnomAD3 genomes

AF:

0.00414

AC:

629

AN:

151888

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0148

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000722

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00101

AC:

248

AN:

244654

Hom.:

AF XY:

0.000708

AC XY:

AN XY:

132718

show subpopulations

Gnomad AFR exome

AF:

0.0149

Gnomad AMR exome

AF:

0.000297

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000689

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000449

Gnomad OTH exome

AF:

0.000337

GnomAD4 exome

AF:

0.000412

AC:

587

AN:

1425206

Hom.:

Cov.:

AF XY:

0.000350

AC XY:

249

AN XY:

710594

show subpopulations

Gnomad4 AFR exome

AF:

0.0158

Gnomad4 AMR exome

AF:

0.000503

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000477

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000120

Gnomad4 OTH exome

AF:

0.000610

GnomAD4 genome

AF:

0.00414

AC:

629

AN:

152004

Hom.:

Cov.:

AF XY:

0.00389

AC XY:

289

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.0147

Gnomad4 AMR

AF:

0.000721

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000656

Hom.:

Bravo

AF:

0.00461

ESP6500AA

AF:

0.0121

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00115

AC:

139

Asia WGS

AF:

0.000867

AC:

AN:

3474

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.17

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Benign

0.35

T;T;T;T

Eigen

Uncertain

0.68

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.80

T;T;.;.

MetaRNN

Benign

0.0065

T;T;T;T

MetaSVM

Uncertain

0.23

MutationAssessor

Uncertain

2.9

M;.;M;M

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.58

PROVEAN

Uncertain

-2.5

D;N;D;D

REVEL

Uncertain

0.29

Sift

Benign

0.041

D;D;D;D

Sift4G

Uncertain

0.039

D;T;D;D

Polyphen

0.76

P;.;P;P

Vest4

0.71

MVP

0.61

MPC

0.34

ClinPred

0.065

GERP RS

5.8

Varity_R

0.70

gMVP

0.38

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over