8-7828846-G-C

Position:

• chr8-7828846-G-C

Variant summary

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

The NM_152251.4(DEFB106A):​c.91G>C​(p.Gly31Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 21)
• Consequence: DEFB106A NM_152251.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.77

Genes affected

DEFB106A (HGNC:18088): (defensin beta 106A) Defensins form a family of antimicrobial and cytotoxic peptides made by neutrophils. Defensins are short, processed peptide molecules that are classified by structure into three groups: alpha-defensins, beta-defensins and theta-defensins. All beta-defensin genes are densely clustered in four to five syntenic chromosomal regions. Chromosome 8p23 contains at least two copies of the duplicated beta-defensin cluster. This duplication results in two identical copies of defensin, beta 106, DEFB106A and DEFB106B, in head-to-head orientation. This gene, DEFB106A, represents the more centromeric copy. [provided by RefSeq, Oct 2014]

LOC124901865 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DEFB106A	NM_152251.4	c.91G>C	p.Gly31Arg	missense_variant	2/2	ENST00000335186.3	NP_689464.1
LOC124901865		n.7828846G>C		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DEFB106A	ENST00000335186.3	c.91G>C	p.Gly31Arg	missense_variant	2/2	1	NM_152251.4	ENSP00000335307.2

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 21

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

May 25, 2022

The c.91G>C (p.G31R) alteration is located in exon 2 (coding exon 2) of the DEFB106A gene. This alteration results from a G to C substitution at nucleotide position 91, causing the glycine (G) at amino acid position 31 to be replaced by an arginine (R). 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	Pathogenic	0.92
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T
Eigen	Benign	0.014
Eigen_PC	Benign	-0.048
FATHMM_MKL	Uncertain	0.82	D
M_CAP	Benign	0.029	D
MetaRNN	Uncertain	0.72	D
MetaSVM	Benign	-0.68	T
PrimateAI	Uncertain	0.51	T
PROVEAN	Pathogenic	-8.0	D
REVEL	Uncertain	0.29
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0050	D
Vest4		0.73
MutPred		0.42		Gain of solvent accessibility (P = 0.0037);
MVP		0.46
MPC		4.1
ClinPred		1.0	D
GERP RS		4.1
Varity_R		0.74
gMVP		0.65

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

Other links and lift over

dbSNP: rs1585691417; hg19: chr8-7686368;