Genetic Variant SCGB2B2:p.Ala13Thr (chr19-34594527-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001025591.4(SCGB2B2):c.37G>A(p.Ala13Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,222 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A13P) has been classified as Uncertain significance.

Frequency

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

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SCGB2B2
NM_001025591.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.145

Variant links:

Genes affected

SCGB2B2 (HGNC:27616): (secretoglobin family 2B member 2) Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

SCGB2B2 links:

SCGB1B2P (HGNC:20741): (secretoglobin family 1B member 2, pseudogene)

SCGB1B2P links:

ZNF807P (HGNC:33229): (zinc finger protein 807, pseudogene)

ZNF807P links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15898788).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCGB2B2	NM_001025591.4 link	c.37G>A	p.Ala13Thr	missense_variant	Exon 2 of 4	ENST00000601241.6	NP_001020762.1	Q4G0G5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SCGB2B2	ENST00000601241.6 link	c.37G>A	p.Ala13Thr	missense_variant	Exon 2 of 4	2	NM_001025591.4	ENSP00000469876.1	Q4G0G5
SCGB2B2	ENST00000379204.2 link	c.37G>A	p.Ala13Thr	missense_variant	Exon 1 of 3	1		ENSP00000368502.2	Q4G0G5
SCGB2B2	ENST00000595326.1 link	n.373-928G>A		intron_variant	Intron 3 of 3	2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251348

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135840

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:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461222

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726908

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000656

AC:

AN:

152334

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.095

T;T

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.0018

M_CAP

Benign

0.0011

MetaRNN

Benign

0.16

T;T

MetaSVM

Benign

-1.0

PrimateAI

Uncertain

0.52

PROVEAN

Uncertain

-4.0

D;.

REVEL

Benign

0.034

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.81

P;P

Vest4

0.20

MutPred

0.36

Gain of sheet (P = 0.0266);Gain of sheet (P = 0.0266);

MVP

0.014

MPC

0.22

ClinPred

0.45

GERP RS

0.046

Varity_R

0.61

gMVP

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over