rs2301180

Variant names:

• chr10-113858487-T-A
• rs2301180
• NM_198514.4:c.179-41T>A

Your query was ambiguous. Multiple possible variants found:

• chr10-113858487-T-A
• chr10-113858487-T-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_198514.4(NHLRC2):​c.179-41T>A 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)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NHLRC2 NM_198514.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0140
• Publications: 10 publications found

Genes affected

NHLRC2 (HGNC:24731): (NHL repeat containing 2) Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

NHLRC2 Gene-Disease associations (from GenCC):

• fibrosis, neurodegeneration, and cerebral angiomatosis

  Inheritance: AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

LOC124902506 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198514.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NHLRC2	NM_198514.4	MANE Select	c.179-41T>A		intron	N/A	NP_940916.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NHLRC2	ENST00000369301.3	TSL:2 MANE Select	c.179-41T>A		intron	N/A	ENSP00000358307.3	Q8NBF2-1
	NHLRC2	ENST00000918088.1		c.179-41T>A		intron	N/A	ENSP00000588147.1
	NHLRC2	ENST00000866165.1		c.178+3437T>A		intron	N/A	ENSP00000536224.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1269408 Hom.: 0 Cov.: 17 AF XY: 0.00 AC XY: 0 AN XY: 636606

African (AFR) AF: 0.00 AC: 0 AN: 27866

American (AMR) AF: 0.00 AC: 0 AN: 33392

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22360

East Asian (EAS) AF: 0.00 AC: 0 AN: 38284

South Asian (SAS) AF: 0.00 AC: 0 AN: 74246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51128

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5222

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 963538

Other (OTH) AF: 0.00 AC: 0 AN: 53372

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.3
DANN	Benign	0.57
PhyloP100		0.014

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

Other links and lift over

dbSNP: rs2301180; hg19: chr10-115618246;