6-61987841-A-C

Position:

• chr6-61987841-A-C

Variant summary

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

The NM_152688.4(KHDRBS2):​c.337-9629T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.794 in 152,076 control chromosomes in the GnomAD database, including 48,297 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 0.79 (48297 hom., cov: 32)
• Consequence: KHDRBS2 NM_152688.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.791

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 (EAS) allele frequency at 95% confidence interval = 0.821 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KHDRBS2	NM_152688.4	c.337-9629T>G		intron_variant		ENST00000281156.5	NP_689901.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KHDRBS2	ENST00000281156.5	c.337-9629T>G		intron_variant		1	NM_152688.4	ENSP00000281156	P1
KHDRBS2	ENST00000675091.1	c.337-9629T>G		intron_variant, NMD_transcript_variant				ENSP00000502245

Frequencies

GnomAD3 genomes AF: 0.794 AC: 120690 AN: 151958 Hom.: 48257 Cov.: 32

Gnomad AFR AF: 0.704

Gnomad AMI AF: 0.866

Gnomad AMR AF: 0.831

Gnomad ASJ AF: 0.764

Gnomad EAS AF: 0.842

Gnomad SAS AF: 0.746

Gnomad FIN AF: 0.908

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.824

Gnomad OTH AF: 0.789

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

GnomAD4 genome AF: 0.794 AC: 120780 AN: 152076 Hom.: 48297 Cov.: 32 AF XY: 0.797 AC XY: 59280 AN XY: 74348

Gnomad4 AFR AF: 0.704

Gnomad4 AMR AF: 0.831

Gnomad4 ASJ AF: 0.764

Gnomad4 EAS AF: 0.842

Gnomad4 SAS AF: 0.746

Gnomad4 FIN AF: 0.908

Gnomad4 NFE AF: 0.824

Gnomad4 OTH AF: 0.786

Alfa AF: 0.814 Hom.: 116331

Bravo AF: 0.787

Asia WGS AF: 0.772 AC: 2687 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.28
DANN	Benign	0.74

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: rs6455128; hg19: chr6-62697746;