rs522914

Positions:

• chr6-61824593-T-A
• chr6-61824593-T-C

Variant summary

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

The NM_152688.4(KHDRBS2):​c.810+70042A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.596 in 151,948 control chromosomes in the GnomAD database, including 27,242 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 0.60 (27242 hom., cov: 32)
• Consequence: KHDRBS2 NM_152688.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.354

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=-0.79).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KHDRBS2	NM_152688.4	c.810+70042A>T		intron_variant		ENST00000281156.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KHDRBS2	ENST00000281156.5	c.810+70042A>T		intron_variant		1	NM_152688.4	P1
KHDRBS2	ENST00000675091.1	c.810+70042A>T		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.596 AC: 90535 AN: 151828 Hom.: 27202 Cov.: 32

Gnomad AFR AF: 0.649

Gnomad AMI AF: 0.477

Gnomad AMR AF: 0.514

Gnomad ASJ AF: 0.650

Gnomad EAS AF: 0.523

Gnomad SAS AF: 0.678

Gnomad FIN AF: 0.629

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.577

Gnomad OTH AF: 0.568

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

GnomAD4 genome AF: 0.596 AC: 90626 AN: 151948 Hom.: 27242 Cov.: 32 AF XY: 0.599 AC XY: 44485 AN XY: 74262

Gnomad4 AFR AF: 0.649

Gnomad4 AMR AF: 0.514

Gnomad4 ASJ AF: 0.650

Gnomad4 EAS AF: 0.523

Gnomad4 SAS AF: 0.678

Gnomad4 FIN AF: 0.629

Gnomad4 NFE AF: 0.577

Gnomad4 OTH AF: 0.571

Alfa AF: 0.588 Hom.: 3323

Bravo AF: 0.588

Asia WGS AF: 0.653 AC: 2270 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.8
DANN	Benign	0.81

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: rs522914; hg19: chr6-62534498;