Variant 9-104102043-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_006444.3(SMC2):c.720G>T(p.Leu240Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00050 ( 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: 0.359

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 Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1854971).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMC2	NM_006444.3 linkuse as main transcript	c.720G>T	p.Leu240Phe	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.720G>T	p.Leu240Phe	missense_variant	8/25	1	NM_006444.3	P1	O95347-1
SMC2	ENST00000286398.11 linkuse as main transcript	c.720G>T	p.Leu240Phe	missense_variant	8/25	1		P1	O95347-1
SMC2	ENST00000374787.7 linkuse as main transcript	c.720G>T	p.Leu240Phe	missense_variant	8/25	2		P1	O95347-1
SMC2	ENST00000440179.5 linkuse as main transcript	c.285G>T	p.Leu95Phe	missense_variant	6/6	3

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

151024

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:

0.000499

AC:

686

AN:

1375840

Hom.:

Cov.:

AF XY:

0.000452

AC XY:

310

AN XY:

686550

show subpopulations

Gnomad4 AFR exome

AF:

0.000801

Gnomad4 AMR exome

AF:

0.000139

Gnomad4 ASJ exome

AF:

0.000375

Gnomad4 EAS exome

AF:

0.000498

Gnomad4 SAS exome

AF:

0.000130

Gnomad4 FIN exome

AF:

0.000585

Gnomad4 NFE exome

AF:

0.000523

Gnomad4 OTH exome

AF:

0.000661

GnomAD4 genome

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

AF:

0.00

AC:

AN:

151150

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73872

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

Feb 14, 2023

The c.720G>T (p.L240F) 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 720, causing the leucine (L) at amino acid position 240 to be replaced by a phenylalanine (F). 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

0.18

BayesDel_addAF

Benign

-0.049

BayesDel_noAF

Benign

-0.31

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.18

T;T;T;T

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.19

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.80

T;T;.;.

M_CAP

Benign

0.018

MetaRNN

Benign

0.19

T;T;T;T

MetaSVM

Benign

-0.77

MutationAssessor

Benign

0.69

N;.;N;N

MutationTaster

Benign

0.53

N;N;N;N

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-1.5

N;N;N;N

REVEL

Benign

0.20

Sift

Benign

0.080

T;T;T;T

Sift4G

Benign

0.13

T;T;T;T

Polyphen

0.0020

B;.;B;B

Vest4

0.30

MutPred

0.49

Loss of disorder (P = 0.1976);.;Loss of disorder (P = 0.1976);Loss of disorder (P = 0.1976);

MVP

0.31

MPC

0.13

ClinPred

0.49

GERP RS

3.1

Varity_R

0.084

gMVP

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over