rs777723610

Variant names:

• chr6-61681019-G-A
• rs777723610
• NM_152688.4:c.994C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-61681019-G-A
• chr6-61681019-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_152688.4(KHDRBS2):​c.994C>T​(p.Pro332Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,934 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P332T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: KHDRBS2 NM_152688.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.23

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]

KHDRBS2-OT1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KHDRBS2	NM_152688.4	c.994C>T	p.Pro332Ser	missense_variant	Exon 9 of 9	ENST00000281156.5	NP_689901.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KHDRBS2	ENST00000281156.5	c.994C>T	p.Pro332Ser	missense_variant	Exon 9 of 9	1	NM_152688.4	ENSP00000281156.3
KHDRBS2-OT1	ENST00000511849.2	n.31C>T		non_coding_transcript_exon_variant	Exon 1 of 6	3
KHDRBS2	ENST00000675091.1	n.*150C>T		non_coding_transcript_exon_variant	Exon 10 of 10			ENSP00000502245.1
KHDRBS2	ENST00000675091.1	n.*150C>T		3_prime_UTR_variant	Exon 10 of 10			ENSP00000502245.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459934 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726360

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.00027	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.043	D
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-0.65	T
MutationAssessor	Uncertain	2.5	M
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-4.2	D
REVEL	Benign	0.26
Sift	Uncertain	0.020	D
Sift4G	Benign	0.26	T
Polyphen		1.0	D
Vest4		0.35
MutPred		0.34		Loss of catalytic residue at P332 (P = 0.0048);
MVP		0.61
MPC		0.31
ClinPred		0.99	D
GERP RS		4.2
Varity_R		0.27
gMVP		0.56

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: rs777723610; hg19: chr6-62390924;