rs10484619

chr6-62149908-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152688.4(KHDRBS2):c.219+27277C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0798 in 152,178 control chromosomes in the GnomAD database, including 521 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.080 (521 hom., cov: 33)
• Consequence: KHDRBS2 NM_152688.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13

Genes affected

KHDRBS2 (HGNC:18114): (KH RNA binding domain containing, signal transduction associated 2) Predicted to enable mRNA binding activity and poly(A) binding activity. Predicted to be involved in regulation of alternative mRNA splicing, via spliceosome. Predicted to be located in nucleoplasm. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KHDRBS2	NM_152688.4	c.219+27277C>T		intron_variant		ENST00000281156.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KHDRBS2	ENST00000281156.5	c.219+27277C>T		intron_variant		1	NM_152688.4	P1
KHDRBS2	ENST00000675091.1	c.219+27277C>T		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0799 AC: 12144 AN: 152060 Hom.: 521 Cov.: 33

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.0628

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.0385

Gnomad SAS AF: 0.0469

Gnomad FIN AF: 0.0818

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0707

Gnomad OTH AF: 0.0789

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0798 AC: 12137 AN: 152178 Hom.: 521 Cov.: 33 AF XY: 0.0793 AC XY: 5901 AN XY: 74396

Gnomad4 AFR AF: 0.104

Gnomad4 AMR AF: 0.0626

Gnomad4 ASJ AF: 0.161

Gnomad4 EAS AF: 0.0386

Gnomad4 SAS AF: 0.0469

Gnomad4 FIN AF: 0.0818

Gnomad4 NFE AF: 0.0707

Gnomad4 OTH AF: 0.0781

Alfa AF: 0.0781 Hom.: 100

Bravo AF: 0.0798

Asia WGS AF: 0.0510 AC: 175 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.88
Dann	Benign	0.54

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: rs10484619; hg19: chr6-62859813;