Genetic Variant SPIN2B:p.His213Gln (chrX-57119991-A-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001006681.2(SPIN2B):c.639T>A(p.His213Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000019 in 1,207,519 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 10 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000091 ( 0 hom., 1 hem., cov: 20)

Exomes 𝑓: 0.000020 ( 0 hom. 9 hem. )

Consequence

SPIN2B
NM_001006681.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.01

Variant links:

Genes affected

SPIN2B (HGNC:33147): (spindlin family member 2B) Enables methylated histone binding activity. Predicted to be involved in regulation of transcription, DNA-templated. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

SPIN2B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.041706264).

BS2

High Hemizygotes in GnomAdExome4 at 9 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPIN2B	NM_001006681.2 link	c.639T>A	p.His213Gln	missense_variant	Exon 2 of 2	ENST00000434397.3	NP_001006682.1	Q9BPZ2A0A024R9Y9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPIN2B	ENST00000434397.3 link	c.639T>A	p.His213Gln	missense_variant	Exon 2 of 2	1	NM_001006681.2	ENSP00000404314.2		Q9BPZ2Q5JZB8

Frequencies

GnomAD3 genomes

AF:

0.00000915

AC:

AN:

109298

Hom.:

Cov.:

AF XY:

0.0000317

AC XY:

AN XY:

31580

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:

0.000292

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

GnomAD3 exomes

AF:

0.0000550

AC:

AN:

181832

Hom.:

AF XY:

0.0000753

AC XY:

AN XY:

66428

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000724

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000200

AC:

AN:

1098169

Hom.:

Cov.:

AF XY:

0.0000248

AC XY:

AN XY:

363523

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000530

Gnomad4 SAS exome

AF:

0.0000370

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000237

Gnomad4 OTH exome

AF:

0.0000434

GnomAD4 genome

AF:

0.00000914

AC:

AN:

109350

Hom.:

Cov.:

AF XY:

0.0000316

AC XY:

AN XY:

31642

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000293

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000227

ExAC

AF:

0.0000494

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 29, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.639T>A (p.H213Q) alteration is located in exon 2 (coding exon 1) of the SPIN2B gene. This alteration results from a T to A substitution at nucleotide position 639, causing the histidine (H) at amino acid position 213 to be replaced by a glutamine (Q). 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

Uncertain

0.39

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Benign

0.73

DEOGEN2

Benign

0.0091

.;T;T;.

FATHMM_MKL

Benign

0.42

LIST_S2

Benign

0.73

T;.;T;T

M_CAP

Benign

0.0046

MetaRNN

Benign

0.042

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.1

.;N;N;.

PrimateAI

Pathogenic

0.79

PROVEAN

Benign

0.43

N;N;N;N

REVEL

Benign

0.17

Sift

Benign

0.53

T;T;T;T

Sift4G

Benign

0.34

T;T;T;.

Polyphen

0.91

.;P;P;.

Vest4

0.17

MutPred

0.34

.;Gain of catalytic residue at H213 (P = 0.0678);Gain of catalytic residue at H213 (P = 0.0678);Gain of catalytic residue at H213 (P = 0.0678);

MVP

0.46

MPC

1.8

ClinPred

0.12

GERP RS

1.4

Varity_R

0.17

gMVP

0.24

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