rs2824499

Variant names:

• chr21-17806954-C-G
• rs2824499
• NM_001100420.2:c.128-9836G>C

Your query was ambiguous. Multiple possible variants found:

• chr21-17806954-C-G
• chr21-17806954-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001100420.2(C21orf91):​c.128-9836G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: C21orf91 NM_001100420.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0530

Genes affected

C21orf91 (HGNC:16459): (chromosome 21 open reading frame 91) Predicted to be involved in cerebral cortex neuron differentiation and positive regulation of dendritic spine development. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000244676 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C21orf91	NM_001100420.2	c.128-9836G>C		intron_variant	Intron 2 of 4	ENST00000284881.9	NP_001093890.1
C21orf91	NM_017447.4	c.128-9836G>C		intron_variant	Intron 2 of 4		NP_059143.3
C21orf91	NM_001100421.2	c.128-9836G>C		intron_variant	Intron 2 of 3		NP_001093891.1
LOC124900465	XR_007067823.1	n.1605+50165C>G		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C21orf91	ENST00000284881.9	c.128-9836G>C		intron_variant	Intron 2 of 4	2	NM_001100420.2	ENSP00000284881.4

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.80
DANN	Benign	0.69

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: rs2824499; hg19: chr21-19179271;