19-34594559-C-T

Position:

• chr19-34594559-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001025591.4(SCGB2B2):​c.5G>A​(p.Arg2Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,268 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SCGB2B2 NM_001025591.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.145

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 (HGNC:):

ACMG classification

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=0.105823696).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCGB2B2	NM_001025591.4	c.5G>A	p.Arg2Lys	missense_variant	2/4	ENST00000601241.6	NP_001020762.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCGB2B2	ENST00000601241.6	c.5G>A	p.Arg2Lys	missense_variant	2/4	2	NM_001025591.4	ENSP00000469876.1
SCGB2B2	ENST00000379204.2	c.5G>A	p.Arg2Lys	missense_variant	1/3	1		ENSP00000368502.2
SCGB2B2	ENST00000595326.1	n.373-960G>A		intron_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460268 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726434

Gnomad4 AFR exome AF: 0.0000299

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 29, 2023

The c.5G>A (p.R2K) alteration is located in exon 1 (coding exon 1) of the SCGB2B2 gene. This alteration results from a G to A substitution at nucleotide position 5, causing the arginine (R) at amino acid position 2 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	0.15
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	11
DANN	Benign	0.50
DEOGEN2	Benign	0.064	T;T
Eigen	Benign	-0.99
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0017	N
M_CAP	Benign	0.0010	T
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-0.99	T
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-3.0	D;.
REVEL	Benign	0.021
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.14	B;B
Vest4		0.13
MutPred		0.18		Gain of ubiquitination at R2 (P = 0.0192);Gain of ubiquitination at R2 (P = 0.0192);
MVP		0.014
MPC		0.095
ClinPred		0.10	T
GERP RS		0.046
Varity_R		0.52
gMVP		0.42

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-35085464;