Variant 9-104102029-G-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_006444.3(SMC2):c.706G>T(p.Ala236Ser) variant causes a missense change involving the alteration of a conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00082 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SMC2
NM_006444.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.82

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 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMC2	NM_006444.3 linkuse as main transcript	c.706G>T	p.Ala236Ser	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.706G>T	p.Ala236Ser	missense_variant	8/25	1	NM_006444.3	P1	O95347-1
SMC2	ENST00000286398.11 linkuse as main transcript	c.706G>T	p.Ala236Ser	missense_variant	8/25	1		P1	O95347-1
SMC2	ENST00000374787.7 linkuse as main transcript	c.706G>T	p.Ala236Ser	missense_variant	8/25	2		P1	O95347-1
SMC2	ENST00000440179.5 linkuse as main transcript	c.271G>T	p.Ala91Ser	missense_variant	6/6	3

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

150856

Hom.:

Cov.:

FAILED QC

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000816

AC:

1110

AN:

1359828

Hom.:

Cov.:

AF XY:

0.000784

AC XY:

532

AN XY:

678754

show subpopulations

Gnomad4 AFR exome

AF:

0.00110

Gnomad4 AMR exome

AF:

0.000464

Gnomad4 ASJ exome

AF:

0.00123

Gnomad4 EAS exome

AF:

0.00152

Gnomad4 SAS exome

AF:

0.000225

Gnomad4 FIN exome

AF:

0.00105

Gnomad4 NFE exome

AF:

0.000820

Gnomad4 OTH exome

AF:

0.000997

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

150972

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73790

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:

0.00

Gnomad4 OTH

AF:

0.00

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

Mar 06, 2023

The c.706G>T (p.A236S) alteration is located in exon 8 (coding exon 7) of the SMC2 gene. This alteration results from a G to T substitution at nucleotide position 706, causing the alanine (A) at amino acid position 236 to be replaced by a serine (S). 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

0.27

BayesDel_addAF

Pathogenic

0.23

BayesDel_noAF

Uncertain

0.090

Cadd

Pathogenic

Dann

Uncertain

1.0

DEOGEN2

Uncertain

0.51

D;T;D;D

Eigen

Pathogenic

0.85

Eigen_PC

Pathogenic

0.87

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.90

D;D;.;.

M_CAP

Benign

0.036

MetaRNN

Uncertain

0.68

D;D;D;D

MetaSVM

Uncertain

0.11

MutationAssessor

Uncertain

2.4

M;.;M;M

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.61

PROVEAN

Uncertain

-2.6

D;D;D;D

REVEL

Uncertain

0.59

Sift

Benign

0.32

T;D;T;T

Sift4G

Benign

0.10

T;T;T;T

Polyphen

0.99

D;.;D;D

Vest4

0.73

MutPred

0.47

Gain of phosphorylation at S231 (P = 0.1344);.;Gain of phosphorylation at S231 (P = 0.1344);Gain of phosphorylation at S231 (P = 0.1344);

MVP

0.63

MPC

0.54

ClinPred

0.97

GERP RS

5.9

Varity_R

0.59

gMVP

0.40

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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