6-61829844-G-A

Position:

• chr6-61829844-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.810+64791C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.648 in 151,912 control chromosomes in the GnomAD database, including 33,000 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 0.65 (33000 hom., cov: 31)
• Consequence: KHDRBS2 NM_152688.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.548

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.822 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KHDRBS2	NM_152688.4	c.810+64791C>T		intron_variant		ENST00000281156.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KHDRBS2	ENST00000281156.5	c.810+64791C>T		intron_variant		1	NM_152688.4	P1
KHDRBS2	ENST00000675091.1	c.810+64791C>T		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.648 AC: 98371 AN: 151794 Hom.: 32941 Cov.: 31

Gnomad AFR AF: 0.829

Gnomad AMI AF: 0.478

Gnomad AMR AF: 0.532

Gnomad ASJ AF: 0.650

Gnomad EAS AF: 0.524

Gnomad SAS AF: 0.680

Gnomad FIN AF: 0.631

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.578

Gnomad OTH AF: 0.602

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

GnomAD4 genome AF: 0.648 AC: 98485 AN: 151912 Hom.: 33000 Cov.: 31 AF XY: 0.648 AC XY: 48129 AN XY: 74226

Gnomad4 AFR AF: 0.829

Gnomad4 AMR AF: 0.532

Gnomad4 ASJ AF: 0.650

Gnomad4 EAS AF: 0.524

Gnomad4 SAS AF: 0.679

Gnomad4 FIN AF: 0.631

Gnomad4 NFE AF: 0.578

Gnomad4 OTH AF: 0.605

Alfa AF: 0.621 Hom.: 5374

Bravo AF: 0.647

Asia WGS AF: 0.664 AC: 2308 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.86
DANN	Benign	0.61

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: rs565795; hg19: chr6-62539749;