6-61976913-G-A

Position:

• chr6-61976913-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000281156.5(KHDRBS2):​c.483+1153C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0156 in 152,232 control chromosomes in the GnomAD database, including 30 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 0.016 (30 hom., cov: 32)
• Consequence: KHDRBS2 ENST00000281156.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.511

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=-0.81).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0156 (2379/152232) while in subpopulation NFE AF= 0.0264 (1795/68010). AF 95% confidence interval is 0.0254. There are 30 homozygotes in gnomad4. There are 1054 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 30 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KHDRBS2	NM_152688.4	c.483+1153C>T		intron_variant		ENST00000281156.5	NP_689901.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KHDRBS2	ENST00000281156.5	c.483+1153C>T		intron_variant		1	NM_152688.4	ENSP00000281156	P1
KHDRBS2	ENST00000675091.1	c.483+1153C>T		intron_variant, NMD_transcript_variant				ENSP00000502245

Frequencies

GnomAD3 genomes AF: 0.0156 AC: 2378 AN: 152114 Hom.: 30 Cov.: 32

Gnomad AFR AF: 0.00471

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0110

Gnomad ASJ AF: 0.0193

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00558

Gnomad FIN AF: 0.00952

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.0264

Gnomad OTH AF: 0.0110

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

GnomAD4 genome AF: 0.0156 AC: 2379 AN: 152232 Hom.: 30 Cov.: 32 AF XY: 0.0142 AC XY: 1054 AN XY: 74426

Gnomad4 AFR AF: 0.00469

Gnomad4 AMR AF: 0.0109

Gnomad4 ASJ AF: 0.0193

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00559

Gnomad4 FIN AF: 0.00952

Gnomad4 NFE AF: 0.0264

Gnomad4 OTH AF: 0.0109

Alfa AF: 0.0208 Hom.: 11

Bravo AF: 0.0150

Asia WGS AF: 0.00145 AC: 5 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.5
DANN	Benign	0.78

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: rs10484621; hg19: chr6-62686818;