Variant 9-104095434-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006444.3(SMC2):c.50G>A(p.Arg17Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,758 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SMC2
NM_006444.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.70

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMC2	NM_006444.3 linkuse as main transcript	c.50G>A	p.Arg17Lys	missense_variant	2/25	ENST00000374793.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMC2	ENST00000374793.8 linkuse as main transcript	c.50G>A	p.Arg17Lys	missense_variant	2/25	1	NM_006444.3	P1	O95347-1
SMC2	ENST00000286398.11 linkuse as main transcript	c.50G>A	p.Arg17Lys	missense_variant	2/25	1		P1	O95347-1
SMC2	ENST00000374787.7 linkuse as main transcript	c.50G>A	p.Arg17Lys	missense_variant	2/25	2		P1	O95347-1
SMC2	ENST00000440179.5 linkuse as main transcript	c.-118+986G>A		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251434

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135884

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461578

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727118

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152180

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000312

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 30, 2021

The c.50G>A (p.R17K) alteration is located in exon 2 (coding exon 1) of the SMC2 gene. This alteration results from a G to A substitution at nucleotide position 50, causing the arginine (R) at amino acid position 17 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Uncertain

0.048

BayesDel_noAF

Benign

-0.17

Cadd

Pathogenic

Dann

Uncertain

1.0

DEOGEN2

Benign

0.30

T;T;T

Eigen

Pathogenic

0.80

Eigen_PC

Pathogenic

0.79

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.94

D;.;.

M_CAP

Benign

0.0050

MetaRNN

Uncertain

0.65

D;D;D

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.7

M;M;M

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.77

PROVEAN

Uncertain

-2.5

D;D;D

REVEL

Benign

0.28

Sift

Uncertain

0.011

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

0.99

D;D;D

Vest4

0.71

MutPred

0.57

Gain of ubiquitination at R17 (P = 0.0162);Gain of ubiquitination at R17 (P = 0.0162);Gain of ubiquitination at R17 (P = 0.0162);

MVP

0.60

MPC

0.55

ClinPred

0.97

GERP RS

5.0

Varity_R

0.77

gMVP

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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