rs202103389

Variant names:

• chr1-222522829-A-C
• NM_024746.4:c.1947T>G

Your query was ambiguous. Multiple possible variants found:

• chr1-222522829-A-C
• chr1-222522829-A-G
• chr1-222522829-A-T

Variant summary

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

The NM_024746.4(HHIPL2):​c.1947T>G​(p.Ser649Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: HHIPL2 NM_024746.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50

Genes affected

HHIPL2 (HGNC:25842): (HHIP like 2) Predicted to enable catalytic activity. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

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 (MetaRNN=0.04668498).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HHIPL2	NM_024746.4	c.1947T>G	p.Ser649Arg	missense_variant	Exon 9 of 9	ENST00000343410.7	NP_079022.2
HHIPL2	XM_024449814.2	c.2004T>G	p.Ser668Arg	missense_variant	Exon 10 of 10		XP_024305582.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HHIPL2	ENST00000343410.7	c.1947T>G	p.Ser649Arg	missense_variant	Exon 9 of 9	1	NM_024746.4	ENSP00000342118.6
HHIPL2	ENST00000468172.1	n.566T>G		non_coding_transcript_exon_variant	Exon 5 of 5	1
HHIPL2	ENST00000473144.5	n.609T>G		non_coding_transcript_exon_variant	Exon 4 of 4	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461878 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727242

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: 0.00000450

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.0090
DANN	Benign	0.50
DEOGEN2	Benign	0.0042	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.25	T
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.047	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.55	N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.83	N
REVEL	Benign	0.011
Sift	Benign	0.37	T
Sift4G	Benign	0.63	T
Polyphen		0.0	B
Vest4		0.11
MutPred		0.24		Gain of MoRF binding (P = 0.0075);
MVP		0.014
MPC		0.19
ClinPred		0.062	T
GERP RS		-3.5
Varity_R		0.042
gMVP		0.38

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-222696171;