2-197743126-G-A

Variant names:

• chr2-197743126-G-A
• rs762920202
• NM_033030.6:c.763C>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_033030.6(BOLL):​c.763C>T​(p.His255Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000138 in 1,452,120 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: BOLL NM_033030.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.17

Genes affected

BOLL (HGNC:14273): (boule homolog, RNA binding protein) This gene belongs to the DAZ gene family required for germ cell development. It encodes an RNA-binding protein which is more similar to Drosophila Boule than to human proteins encoded by genes DAZ (deleted in azoospermia) or DAZL (deleted in azoospermia-like). Loss of this gene function results in the absence of sperm in semen (azoospermia). Histological studies demonstrated that the primary defect is at the meiotic G2/M transition. Two alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ENSG00000222017 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37003785).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BOLL	NM_033030.6	c.763C>T	p.His255Tyr	missense_variant	Exon 10 of 11	ENST00000392296.9	NP_149019.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BOLL	ENST00000392296.9	c.763C>T	p.His255Tyr	missense_variant	Exon 10 of 11	1	NM_033030.6	ENSP00000376116.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000814 AC: 2 AN: 245822 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 133344

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000613

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1452120 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 722672

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000466

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

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 25, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.799C>T (p.H267Y) alteration is located in exon 10 (coding exon 10) of the BOLL gene. This alteration results from a C to T substitution at nucleotide position 799, causing the histidine (H) at amino acid position 267 to be replaced by a tyrosine (Y). 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	-0.068	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.034	T;T;.;.;T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.83	T;.;T;T;T
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.37	T;T;T;T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	0.26	.;N;.;.;N
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.6	N;N;D;N;N
REVEL	Benign	0.27
Sift	Uncertain	0.0020	D;D;D;D;D
Sift4G	Benign	0.090	T;T;T;T;T
Polyphen		0.85, 0.96	.;P;.;D;P
Vest4		0.52
MutPred		0.35		.;Gain of phosphorylation at H255 (P = 0.0378);.;.;Gain of phosphorylation at H255 (P = 0.0378);
MVP		0.29
MPC		0.36
ClinPred		0.72	D
GERP RS		5.3
Varity_R		0.22
gMVP		0.73

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: rs762920202; hg19: chr2-198607850;