2-197743076-C-A

Variant names:

• chr2-197743076-C-A
• NM_033030.6:c.813G>T
• BOLL p.Gln271His

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_033030.6(BOLL):​c.813G>T​(p.Gln271His) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: BOLL NM_033030.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.26
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23715883).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033030.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BOLL	NM_033030.6	MANE Select	c.813G>T	p.Gln271His	missense	Exon 10 of 11	NP_149019.1	Q8N9W6-1
	BOLL	NM_001284361.2		c.897G>T	p.Gln299His	missense	Exon 11 of 12	NP_001271290.1	Q8N9W6-2
	BOLL	NM_197970.3		c.849G>T	p.Gln283His	missense	Exon 10 of 11	NP_932074.1	Q8N9W6-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BOLL	ENST00000392296.9	TSL:1 MANE Select	c.813G>T	p.Gln271His	missense	Exon 10 of 11	ENSP00000376116.4	Q8N9W6-1
	BOLL	ENST00000433157.1	TSL:1	c.813G>T	p.Gln271His	missense	Exon 10 of 11	ENSP00000396099.1	Q8N9W6-1
	ENSG00000222017	ENST00000409845.1	TSL:1	n.167-28781C>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1444582 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 718756

African (AFR) AF: 0.00 AC: 0 AN: 32950

American (AMR) AF: 0.00 AC: 0 AN: 41172

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25758

East Asian (EAS) AF: 0.00 AC: 0 AN: 39074

South Asian (SAS) AF: 0.00 AC: 0 AN: 83028

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53080

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5712

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1104312

Other (OTH) AF: 0.00 AC: 0 AN: 59496

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.057	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.032	T
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.97	L
PhyloP100		1.3
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.26
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.089	T
Varity_R		0.36
gMVP		0.66
Mutation Taster		=92/8	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr2-198607800;