20-259269-G-C

Position:

• chr20-259269-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_207469.3(DEFB132):​c.251G>C​(p.Arg84Thr) 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DEFB132 NM_207469.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.181

Genes affected

DEFB132 (HGNC:33806): (defensin beta 132) Defensins are cysteine-rich cationic polypeptides that are important in the immunologic response to invading microorganisms. The protein encoded by this gene is secreted and is a member of the beta defensin protein family. This protein binds spermatozoa and has antimicrobial activity against E. coli. Beta defensin genes are found in several clusters throughout the genome, with this gene mapping to a cluster at 20p13. [provided by RefSeq, Nov 2014]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.054254502).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DEFB132	NM_207469.3	c.251G>C	p.Arg84Thr	missense_variant	2/2	ENST00000382376.4	NP_997352.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DEFB132	ENST00000382376.4	c.251G>C	p.Arg84Thr	missense_variant	2/2	1	NM_207469.3	ENSP00000371813.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1458922 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 725834

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

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

Aug 30, 2021

The c.251G>C (p.R84T) alteration is located in exon 2 (coding exon 2) of the DEFB132 gene. This alteration results from a G to C substitution at nucleotide position 251, causing the arginine (R) at amino acid position 84 to be replaced by a threonine (T). 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	0.12
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.3
DANN	Benign	0.66
DEOGEN2	Benign	0.0037	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.054	T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-0.37	N
REVEL	Benign	0.010
Sift	Benign	0.11	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.43	B
Vest4		0.12
MutPred		0.15		Loss of helix (P = 0.0196);
MVP		0.040
MPC		0.14
ClinPred		0.081	T
GERP RS		-1.2
Varity_R		0.066
gMVP		0.099

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: chr20-239910;