19-34594353-G-T

Variant names:

• chr19-34594353-G-T
• NM_001025591.4:c.68C>A

Variant summary

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

The NM_001025591.4(SCGB2B2):​c.68C>A​(p.Ala23Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SCGB2B2 NM_001025591.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.171

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]

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

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

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=0.21958697).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCGB2B2	NM_001025591.4	c.68C>A	p.Ala23Asp	missense_variant	Exon 3 of 4	ENST00000601241.6	NP_001020762.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCGB2B2	ENST00000601241.6	c.68C>A	p.Ala23Asp	missense_variant	Exon 3 of 4	2	NM_001025591.4	ENSP00000469876.1
SCGB2B2	ENST00000379204.2	c.68C>A	p.Ala23Asp	missense_variant	Exon 2 of 3	1		ENSP00000368502.2
SCGB2B2	ENST00000595326.1	n.373-754C>A		intron_variant	Intron 3 of 3	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 18, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.68C>A (p.A23D) alteration is located in exon 2 (coding exon 2) of the SCGB2B2 gene. This alteration results from a C to A substitution at nucleotide position 68, causing the alanine (A) at amino acid position 23 to be replaced by an aspartic acid (D). 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	0.47
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	16
DANN	Benign	0.83
DEOGEN2	Benign	0.028	T;T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.0046	N
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.22	T;T
MetaSVM	Benign	-0.98	T
PrimateAI	Uncertain	0.52	T
PROVEAN	Pathogenic	-6.0	D;.
REVEL	Benign	0.019
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.91	P;P
Vest4		0.32
MutPred		0.27		Loss of helix (P = 0.0376);Loss of helix (P = 0.0376);
MVP		0.030
MPC		0.30
ClinPred		0.36	T
GERP RS		0.046
Varity_R		0.87
gMVP		0.43

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-35085258;