chr6-62065970-A-G

Position:

• chr6-62065970-A-G

Variant summary

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

The NM_152688.4(KHDRBS2):​c.220-17976T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0782 in 151,628 control chromosomes in the GnomAD database, including 503 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 0.078 (503 hom., cov: 31)
• Consequence: KHDRBS2 NM_152688.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0360

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0947 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KHDRBS2	NM_152688.4	c.220-17976T>C		intron_variant		ENST00000281156.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KHDRBS2	ENST00000281156.5	c.220-17976T>C		intron_variant		1	NM_152688.4	P1
KHDRBS2	ENST00000675091.1	c.220-17976T>C		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0783 AC: 11862 AN: 151510 Hom.: 503 Cov.: 31

Gnomad AFR AF: 0.0975

Gnomad AMI AF: 0.0176

Gnomad AMR AF: 0.0627

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.0380

Gnomad SAS AF: 0.0481

Gnomad FIN AF: 0.0824

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0712

Gnomad OTH AF: 0.0785

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

GnomAD4 genome AF: 0.0782 AC: 11859 AN: 151628 Hom.: 503 Cov.: 31 AF XY: 0.0780 AC XY: 5777 AN XY: 74076

Gnomad4 AFR AF: 0.0972

Gnomad4 AMR AF: 0.0625

Gnomad4 ASJ AF: 0.160

Gnomad4 EAS AF: 0.0381

Gnomad4 SAS AF: 0.0482

Gnomad4 FIN AF: 0.0824

Gnomad4 NFE AF: 0.0712

Gnomad4 OTH AF: 0.0777

Alfa AF: 0.0740 Hom.: 237

Bravo AF: 0.0779

Asia WGS AF: 0.0500 AC: 172 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.6
DANN	Benign	0.86

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: rs10484620; hg19: chr6-62775875;