9-5919782-G-A

Position:

• chr9-5919782-G-A

Variant summary

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

The NM_001017969.3(BRD10):​c.6214C>T​(p.Leu2072Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,522 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: BRD10 NM_001017969.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.11

Genes affected

BRD10 (HGNC:23378): (bromodomain containing 10)

BRD10 (HGNC:):

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=0.10346368).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRD10	NM_001017969.3	c.6214C>T	p.Leu2072Phe	missense_variant	8/8	ENST00000399933.8	NP_001017969.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIAA2026	ENST00000399933.8	c.6214C>T	p.Leu2072Phe	missense_variant	8/8	5	NM_001017969.3	ENSP00000382815.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461522 Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1 AN XY: 727046

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: 0.0000166

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Oct 20, 2023

The c.6214C>T (p.L2072F) alteration is located in exon 8 (coding exon 8) of the KIAA2026 gene. This alteration results from a C to T substitution at nucleotide position 6214, causing the leucine (L) at amino acid position 2072 to be replaced by a phenylalanine (F). 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	0.073
BayesDel_addAF	Benign	-0.092	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.041	T;.
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.11
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.71	T;T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.10	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L;.
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.37	N;N
REVEL	Benign	0.057
Sift	Benign	0.22	T;T
Sift4G	Benign	0.57	T;T
Polyphen		0.011	B;.
Vest4		0.29
MutPred		0.34		Gain of sheet (P = 0.0477);.;
MVP		0.21
ClinPred		0.67	D
GERP RS		3.1
Varity_R		0.056
gMVP		0.15

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: rs1833880531; hg19: chr9-5919782;